Author: "Patrice Chevallier" / Publisher: hal ccsd - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Patrice Chevallier"' showing total 62 results

Start Over Author "Patrice Chevallier" Publisher hal ccsd

62 results on '"Patrice Chevallier"'

1. Anti‐SARS‐CoV‐2 vaccines in recipient and/or donor before allotransplant

Author: Maxime Jullien, Marianne Coste‐Burel, Beatrice Clemenceau, Valentin Letailleur, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Berthe‐Marie Imbert, Jocelyn Ollier, Audrey Grain, Cyrille Touzeau, Philippe Moreau, Marie C Béné, Henri Vié, Patrice Chevallier, Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie [CHU Nantes], Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service d'hématologie biologique [Nantes] (Cytologie Hématologique), Hôtel-Dieu de Nantes-Centre hospitalier universitaire de Nantes (CHU Nantes), and Ollier, Jocelyn
Subjects: allogeneic, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.IMM] Life Sciences [q-bio]/Immunology, viruses, fungi, virus diseases, COVID-19, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, SARS-CoV-2 mRNA, cellular response, surgical procedures, operative, vaccine, [SDV.IMM]Life Sciences [q-bio]/Immunology, hematological, skin and connective tissue diseases, humoral response, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The impact of pre-transplant anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in 20 recipients of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and/or their donors is reported here, showing that the persistence of anti-SARS-CoV-2 antibodies can be detected in almost all patients, whatever the type of vaccine used, and up to 9 months post transplant. Also, an anti-SARS-CoV-2 spike glycoprotein CD3+ T-cell response could be detected in six (35%) of 17 evaluable patients. This study provides a rationale to consider anti-SARS-CoV-2 vaccination of both recipients and donors before Allo-HSCT.
Published: 2022
Full Text: View/download PDF

2. Pooled Fecal Allogenic Microbiotherapy for Refractory Gastrointestinal Acute Graft-Versus-Host Disease: Results from the Early Access Program in France

Author: Florent Malard, Michael Loschi, Thomas Cluzeau, Faezeh Legrand, Jean-Baptiste Mear, Faustine Lhomme, Sarah Guenounou, Anne Huynh, Cecile Borel, Deborah Desmier, Niels Moya, Amandine Charbonnier, Delphine Lebon, Hélène Labussière-Wallet, Corentin Orvain, Sylvain Chantepie, Claude-Eric Bulabois, Vincent Camus, Marie-Anne Couturier, Jérôme Cornillon, Patrice Chevallier, Clémence Mediavilla, Patrice Ceballos, David Beauvais, Marion Bruelle, Emilie Plantamura, Mohamad Mohty, DESSAIVRE, Louise, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Pontchaillou [Rennes], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Grenoble, Université Grenoble Alpes (UGA), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, MaaT Pharma [Lyon], CEREST-TC [CHU Saint-Antoine], and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP]
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction Acute graft-versus-host disease (aGvHD) is a major source of mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Standard 1st line therapy for the treatment of aGvHD involves corticosteroids (CS). However, more than 50% of patients are refractory to CS (SR-aGvHD) and the associated mortality rate is of up to 80%. Recently, Ruxolitinib has been approved as 2nd line treatment for SR-aGvHD. However, patients with severe gastrointestinal (GI) aGvHD seem less likely to respond to Ruxolitinib and have poor outcomes with limited therapeutic options.In this context, fecal microbiotherapy has shown promising results in several pilot studies in patients with refractory GI-aGvHD. Here we report clinical outcomes from 81 patients diagnosed with SR or dependent (SD) GI-aGvHD treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in France.Methods 81 patients with SR/SD GI-aGvHD (Classical n=62, late onset n=12, overlap syndrome n=7) were treated with MaaT013 as part of an EAP in France. These patients had failed 1 to 6 prior systemic GvHD treatment lines (median 2; 66/81 received Ruxolitinib). Most patients had grade III-IV aGvHD (11% grade II, 51% grade III, 38% grade IV).For each patient, a total of 3 MaaT013 administrations were planned every 7 +/- 2 days. Each dose comprised 30g of feces in 150 mL of diluent, from 4 to 8 healthy donors, administered by enema (except for 1 patient by nasogastric tube).Treatment response was calculated among all treated patients based on aGvHD staging and grading at day 28 (D28) at the time of the EAP request.Results At D28, the GI-overall response rate (ORR) was 56%: 30 complete response (CR, 37%), 11 very good response rate (VGPR, 14%), 4 partial response (PR, 5%). The GI-ORR was higher in patients with lower grade aGvHD (89% in grade II, 66% in grade III, 32% in grade IV) and higher in SD versus SR patients (92% versus 49%). Including skin and liver symptoms (n=78), response rate was 49%, including 24 CR, 11 VGPR and 3 PR and inversely correlated with aGvHD initial grade (88% in grade II, 55% in grade III, 30% in grade IV).Overall survival (OS) was 51% at 6 months (M6) and 39% at M12. The median follow-up among surviving patients was 355 days (range, 53-731). OS was significantly higher in patients achieving at least GI-PR at D28 (Responder, R; n=45) compared to patients in treatment failure (Non-responder, NR; n=35): 69% versus 28% at M6, 59% versus 14% at M12, respectively. Median survival duration in R was 451 days versus 32 days in NR.Interestingly, aGvHD response was improved in the subgroup of 31 patients previously treated with Ruxolitinib as 2nd line and MaaT013 as 3rd line (65% D28 GI-ORR, OS M6 55% and 49% M12 and 74% versus 15% at M6 and 74% versus 0% at M12 for R and NR respectively).MaaT013 displayed a good overall safety profile in the EAP population: 20 pharmacovigilance cases were reported in 18 patients: sepsis in 11 patients, C. difficile colitis in 2, E. coli osteoarthritis in 1, G. silvicola in stools from 1, P. aeruginosa sinusitis in 1, appearance of air bubbles in the mesorectum in 1, respiratory distress in 1. No pathogen transmission was reported. In 2 patients, non-pathogenic commensal bacteria isolated following infectious events were detected in the administered MaaT013 batch. Causality could not be formally excluded in these cases.The overall incidence of bacteremia (14%) remains low, compared to an incidence of 31% to 74% in bloodstream infections reported in patients with GI-aGvHD. This suggests that fecal microbiotherapy may have a protective effect on bacterial translocation, but this needs to be confirmed in further clinical trials.47 deaths have been reported; the cause of which was GvHD in 21 patients, severe infection in 13, relapse of underlying malignancy in 6, COVID-19 in 3, hemorrhage during surgery in 1, neurological complications post allo-HCT in 1, and cardiac arrest in 2 patients. No causality link with MaaT013 administration has been identified.Conclusion Overall, EAP clinical data showed that MaaT013 was safe and effective for the treatment of SR/SD-GI-aGvHD especially in patients having previously received ruxolitinib. Interestingly, GI-response to aGvHD correlates with increased OS, suggesting a strong favorable benefit-risk profile for MaaT013. A Phase 3 trial is currently ongoing to confirm these results in ruxolitinib-refractory patients (NCT04769895).
Published: 2022
Full Text: View/download PDF

3. Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation: a retrospective cohort study

Author: Effie W Petersdorf, Mary Carrington, Colm O'hUigin, Mats Bengtsson, Dianne De Santis, Valerie Dubois, Ted Gooley, Mary Horowitz, Katharine Hsu, J Alejandro Madrigal, Martin J Maiers, Mari Malkki, Caroline McKallor, Yasuo Morishima, Machteld Oudshoorn, Stephen R Spellman, Jean Villard, Phil Stevenson, Martin Maiers, Stephen Spellman, Jane Apperley, Peter Bardy, Ghislaine Bernard, Yves Bertrand, Adrian Bloor, Chiara Bonini, Stephane Buhler, Laura Bungener, Helen Campbell, Kristina Carlson, Ben Carpenter, Anne Cesbron, Christian Chabannon, Yves Chalandon, Jeremy Chapman, Réda Chebel, Patrice Chevallier, Gerda Choi, Matt Collin, Jan J Cornelissen, Charles Crawley, Lloyd D'Orsogna, Jean-Hugues Dalle, Eric Deconinck, Muriel DeMatteis, Mary Diviney, Anne Dormoy, Katia Gagne, Brenda Gibson, Maria Gilleece, David Gottlieb, John Gribben, Tayfun Güngör, Mike Haagenson, Cathie Hart, Rhonda Holdsworth, Ian Humphreys, Yoshihisa Kodera, Mickey Koh, Hélène Labussière-Wallet, Arjan C Lankester, Neubery Lardy, Sarah Lawson, Xavier Leleu, Stephen MacKinnon, Ram Malladi, Steven GE Marsh, Murray Martin, Neema P Mayor, I Grant McQuaker, Ellen Meijer, Satoko Morishima, Emmanouil Nikolousis, Kim Orchard, Jacob Passweg, Amit Patel, Katherine Patrick, Béatrice Pedron, Andy Peniket, Julia Perry, Eefke Petersen, Victoria Potter, Mike Potter, Rachel Protheroe, Nicole Raus, Carmen Ruiz de Elvira, Nigel Russell, Nicholaas PM Schaap, Urs Schanz, Harry Schouten, Roderick Skinner, John Snowden, Eric Spierings, Colin Steward, Eleni Tholouli, Alycia Thornton, Marcel Tilanus, Arnold van de Meer, Hendrik Veelkens, Paul Veys, Narelle Watson, Lyanne Weston, Keith Wilson, Marie Wilson, Robert Wynn, József Zsiros, University of Washington [Seattle], Harvard University [Cambridge], Frederick National Laboratory for Cancer Research (FNLCR), Uppsala Universitet [Uppsala], PathWest Murdoch / Fiona Stanley Hospital [Perth, WA, Australia] (PMFSH), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical College of Wisconsin [Milwaukee] (MCW), Memorial Sloane Kettering Cancer Center [New York], Royal Free Hospital [London, UK], Center for International Blood and Marrow Transplant Research [Minneapolis, MN, USA] (CIBMTR), Aichi Medical University School of Medicine [Nagakute, Aichi, Japan] (AMUSM), Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Geneva University Hospital (HUG), International Histocompatibility Working Group in Hematopoietic Cell Transplantation: Effie W Petersdorf, Mary Carrington, Colm O'hUigin, Mats Bengtsson, Dianne De Santis, Valerie Dubois, Ted Gooley, Mary Horowitz, Katharine Hsu, J Alejandro Madrigal, Martin Maiers, Mari Malkki, Caroline McKallor, Yasuo Morishima, Machteld Oudshoorn, Stephen Spellman, Jean Villard, Phil Stevenson, Jane Apperley, Peter Bardy, Ghislaine Bernard, Yves Bertrand, Adrian Bloor, Chiara Bonini, Stephane Buhler, Laura Bungener, Helen Campbell, Kristina Carlson, Ben Carpenter, Anne Cesbron, Christian Chabannon, Yves Chalandon, Jeremy Chapman, Réda Chebel, Patrice Chevallier, Gerda Choi, Matt Collin, Jan J Cornelissen, Charles Crawley, Lloyd D'Orsogna, Jean-Hugues Dalle, Eric Deconinck, Muriel DeMatteis, Mary Diviney, Anne Dormoy, Katia Gagne, Brenda Gibson, Maria Gilleece, David Gottlieb, John Gribben, Tayfun Güngör, Mike Haagenson, Cathie Hart, Rhonda Holdsworth, Ian Humphreys, Yoshihisa Kodera, Mickey Koh, Hélène Labussière-Wallet, Arjan C Lankester, Neubery Lardy, Sarah Lawson, Xavier Leleu, Stephen MacKinnon, Ram Malladi, Steven Ge Marsh, Murray Martin, Neema P Mayor, I Grant McQuaker, Ellen Meijer, Satoko Morishima, Emmanouil Nikolousis, Kim Orchard, Jacob Passweg, Amit Patel, Katherine Patrick, Béatrice Pedron, Andy Peniket, Julia Perry, Eefke Petersen, Victoria Potter, Mike Potter, Rachel Protheroe, Nicole Raus, Carmen Ruiz de Elvira, Nigel Russell, Nicholaas Pm Schaap, Urs Schanz, Harry Schouten, Roderick Skinner, John Snowden, Eric Spierings, Colin Steward, Eleni Tholouli, Alycia Thornton, Marcel Tilanus, Arnold van de Meer, Hendrik Veelkens, Paul Veys, Narelle Watson, Lyanne Weston, Keith Wilson, Marie Wilson, Robert Wynn, József Zsiros, Leiden University Medical Center (LUMC), GAGNE, Katia, CCA - Cancer Treatment and quality of life, AII - Inflammatory diseases, Hematology, CCA - Cancer biology and immunology, Petersdorf, E. W., Carrington, M., O'Huigin, C., Bengtsson, M., De Santis, D., Dubois, V., Gooley, T., Horowitz, M., Hsu, K., Madrigal, J. A., Maiers, M. J., Malkki, M., Mckallor, C., Morishima, Y., Oudshoorn, M., Spellman, S. R., Villard, J., Stevenson, P., Maiers, M., Spellman, S., Apperley, J., Bardy, P., Bernard, G., Bertrand, Y., Bloor, A., Bonini, C., Buhler, S., Bungener, L., Campbell, H., Carlson, K., Carpenter, B., Cesbron, A., Chabannon, C., Chalandon, Y., Chapman, J., Chebel, R., Chevallier, P., Choi, G., Collin, M., Cornelissen, J. J., Crawley, C., D'Orsogna, L., Dalle, J. -H., Deconinck, E., Dematteis, M., Diviney, M., Dormoy, A., Gagne, K., Gibson, B., Gilleece, M., Gottlieb, D., Gribben, J., Gungor, T., Haagenson, M., Hart, C., Holdsworth, R., Humphreys, I., Kodera, Y., Koh, M., Labussiere-Wallet, H., Lankester, A. C., Lardy, N., Lawson, S., Leleu, X., Mackinnon, S., Malladi, R., Marsh, S. G., Martin, M., Mayor, N. P., Mcquaker, I. G., Meijer, E., Morishima, S., Nikolousis, E., Orchard, K., Passweg, J., Patel, A., Patrick, K., Pedron, B., Peniket, A., Perry, J., Petersen, E., Potter, V., Potter, M., Protheroe, R., Raus, N., Ruiz de Elvira, C., Russell, N., Schaap, N. P., Schanz, U., Schouten, H., Skinner, R., Snowden, J., Spierings, E., Steward, C., Tholouli, E., Thornton, A., Tilanus, M., van de Meer, A., Veelkens, H., Veys, P., Watson, N., Weston, L., Wilson, K., Wilson, M., Wynn, R., Zsiros, J., RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: DA TI Staf (9), University of Zurich, and Petersdorf, Effie W
Subjects: Oncology, Male, Hematopoietic Stem Cell Transplantation/methods, [SDV]Life Sciences [q-bio], 2720 Hematology, Graft vs Host Disease, Histocompatibility Testing, 0302 clinical medicine, Graft vs Host Disease/genetics, immune system diseases, unrelated donor, Exons/genetics, graft-versus-host disease, Medicine, ddc:616, Hematopoietic Stem Cell Transplantation, Exons, Hematology, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], surgical procedures, operative, 030220 oncology & carcinogenesis, Histocompatibility, HLA-B Antigens/genetics, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, EXPRESSION, Adult, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, 610 Medicine & health, Human leukocyte antigen, Lower risk, Risk Assessment, Article, Graft vs Host Disease/genetics/immunology, 03 medical and health sciences, Internal medicine, Journal Article, Humans, Retrospective Studies, RECEPTOR, business.industry, MORTALITY, RECOGNITION, Retrospective cohort study, Odds ratio, medicine.disease, Transplantation, Graft-versus-host disease, hematopoietic-cell transplantation, SEQUENCE-DERIVED PEPTIDES, 10036 Medical Clinic, HLA-B Antigens, 10032 Clinic for Oncology and Hematology, Multivariate Analysis, RESIDUES, HLA-B leader, business, 030215 immunology
Abstract: Background: The success of unrelated haemopoietic cell transplantation (HCT) is limited by graft-versus-host disease (GVHD), which is the main post-transplantation challenge when HLA-matched donors are unavailable. A sequence dimorphism in exon 1 of HLA-B gives rise to leader peptides containing methionine (Met; M) or threonine (Thr; T), which differentially influence natural killer and T-cell alloresponses. The main aim of the study was to evaluate the role of the leader dimorphism in GVHD after HLA-B-mismatched unrelated HCT. Methods: We did a retrospective cohort study of 33 982 patients who received an unrelated HCT done in Australia, Europe, Japan, North America, and the UK between Jan 1, 1988, and Dec 31, 2016. Data were contributed by participants of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation. All cases were included and there were no exclusion criteria. Multivariate regression models were used to assess risks associated with HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 mismatching. Among the 33 982 transplantations, the risks of GVHD associated with HLA-B M and T leaders were established in 17 100 (50·3%) HLA-matched and 1457 (4·3%) single HLA-B-mismatched transplantations using multivariate regression models. Leader frequencies were defined in 2 004 742 BeTheMatch US registry donors. Findings: Between Jan 20, 2017, and March 11, 2019, we assessed 33 982 HCTs using multivariate regression models for the role of HLA mismatching on outcome. Median follow-up was 1841 days (IQR 909–2963). Mortality and GVHD increased with increasing numbers of HLA mismatches. A single HLA-B mismatch increased grade 3–4 acute GVHD (odds ratio [OR] 1·89, 95% CI 1·53–2·33; p
Published: 2021
Full Text: View/download PDF

4. Safety and antibody response after one and/or two doses of BNT162b2 Anti‐SARS‐CoV‐2 mRNA vaccine in patients treated by CAR T cells therapy

Author: Anne Lok, Pierre Peterlin, Viviane Dubruille, Steven Le Gouill, Sophie Vanthygem, Marianne Coste-Burel, Patrice Chevallier, Benoit Tessoulin, Berthe-Marie Imbert, Marie C. Béné, Nicolas Blin, Philippe Moreau, Thomas Drumel, Alice Garnier, Thierry Guillaume, Amandine Le Bourgeois, Beatrice Mahe, Maxime Jullien, Thomas Gastinne, Cyrille Touzeau, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Male, Antibodies, Viral, Immunotherapy, Adoptive, Immunogenicity, Vaccine, 0302 clinical medicine, vaccine, Antineoplastic Combined Chemotherapy Protocols, Medicine, CAR‐T cells, 030212 general & internal medicine, Antigens, Viral, ComputingMilieux_MISCELLANEOUS, Receptors, Chimeric Antigen, Lymphoma, Non-Hodgkin, Vaccination, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, SARS-CoV-2 mRNA, Combined Modality Therapy, 3. Good health, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Female, Car t cells, COVID 19, Adult, 2019-20 coronavirus outbreak, Fever, Coronavirus disease 2019 (COVID-19), CAR-T cells, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunization, Secondary, Receptors, Antigen, T-Cell, Pain, [SDV.CAN]Life Sciences [q-bio]/Cancer, SARS‐CoV‐2 mRNA, Immunocompromised Host, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Correspondence, Humans, In patient, BNT162 Vaccine, Aged, Biological Products, Messenger RNA, SARS-CoV-2, business.industry, COVID-19, Virology, Antibody response, Immunoglobulin G, BNT162b2, business
Abstract: International audience; No abstract available
Published: 2021
Full Text: View/download PDF

5. Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients

Author: Patrice Chevallier, Christelle Retière, Katia Gagne, Léa Dubreuil, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), EFS Centre-Pays de la Loire [Nantes], Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: 0301 basic medicine, Cancer Research, Cell, Context (language use), chemical and pharmacologic phenomena, NK-cell-based immunotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human leukocyte antigen, Immunogenetics, Review, Biology, polymorphism, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, Genetic model, medicine, acute leukemia, RC254-282, natural killer cells, Effector, K. Relevance of natural killer cells, hematopoietic stem-cell transplantations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, HLA class I, 3. Good health, killer-cell immunoglobulin-like receptors, Transplantation, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, surgical procedures, operative, Oncology, Immunology, 030215 immunology
Abstract: Simple Summary Immunotherapies are promising approaches to curing different acute leukemias. Natural killer (NK) cells are lymphocytes that are efficient in the elimination of leukemic cells. NK-cell-based immunotherapies are particularly attractive, but the landscape of the heterogeneity of NK cells must be deciphered. This review provides an overview of the polymorphic KIR and HLA class I genes that modulate the NK cell repertoire and how these markers can improve the outcomes of patients with acute leukemia. A better knowledge of these genetic markers that are linked to NK cell subsets that are efficient against hematological diseases will optimize hematopoietic stem-cell donor selection and NK immunotherapy design. Abstract Since the mid-1990s, the biology and functions of natural killer (NK) cells have been deeply investigated in healthy individuals and in people with diseases. These effector cells play a particularly crucial role after allogeneic hematopoietic stem-cell transplantation (HSCT) through their graft-versus-leukemia (GvL) effect, which is mainly mediated through polymorphic killer-cell immunoglobulin-like receptors (KIRs) and their cognates, HLA class I ligands. In this review, we present how KIRs and HLA class I ligands modulate the structural formation and the functional education of NK cells. In particular, we decipher the current knowledge about the extent of KIR and HLA class I gene polymorphisms, as well as their expression, interaction, and functional impact on the KIR+ NK cell repertoire in a physiological context and in a leukemic context. In addition, we present the impact of NK cell alloreactivity on the outcomes of HSCT in adult patients with acute leukemia, as well as a description of genetic models of KIRs and NK cell reconstitution, with a focus on emergent T-cell-repleted haplo-identical HSCT using cyclosphosphamide post-grafting (haplo-PTCy). Then, we document how the immunogenetics of KIR/HLA and the immunobiology of NK cells could improve the relapse incidence after haplo-PTCy. Ultimately, we review the emerging NK-cell-based immunotherapies for leukemic patients in addition to HSCT.
Published: 2021
Full Text: View/download PDF

6. Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial

Author: null Olivier Tournilhac, null Magali Le Garff-Tavernier, null Stéphanie Nguyen Quoc, null Edouard Forcade, null Patrice Chevallier, null Faezeh Legrand-Izadifar, null Gandhi Laurent Damaj, null David Michonneau, null Cécile Tomowiak, null Cécile Borel, null Corentin Orvain, null Pascal Turlure, null Rabah Redjou, null Gaëlle Guillerm, null Laure Vincent, null Celestine Simand, null Richard Lemal, null Claire Quiney, null Patricia Combes, null Bruno Pereira, null Laure Calvet, null Aurélie Cabrespine, null Jacques-Olivier Bay, null Véronique Leblond, null Nathalie Dhédin, French Innovative Leukemia Organization (FILO), Société Francophone de Greffe De Moelle et de Thérapie Cellulaire (SFGM-TC), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)
Subjects: Oncology, medicine.medical_specialty, Neoplasm, Residual, Transplantation Conditioning, Chronic lymphocytic leukemia, medicine.medical_treatment, Phases of clinical research, Graft vs Host Disease, Hematopoietic stem cell transplantation, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Cumulative incidence, Prospective Studies, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Donor Lymphocytes, Minimal residual disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Regimen, Graft-versus-host disease, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing chronic lymphocytic leukemia (CLL). Minimal residual disease (MRD) assessment at 12 months (M12) post-HSCT is predictive of relapse. This phase II study aimed to achieve M12 MRD negativity (MRDneg) using an MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed in case of failure by donor lymphocytes infusions. Patients had high-risk CLL according to the 2006 European Society for Blood and Marrow Transplantation consensus, in complete or partial response with lymphadenopathy
Published: 2021
Full Text: View/download PDF

7. A phase I/II feasibility vaccine study by autologous leukemic apoptotic corpse-pulsed dendritic cells for elderly AML patients

Author: Patrice Chevallier, Nadine Juge-Morineau, Thierry Guillaume, Céline Bossard, Marie C. Béné, Pierre Peterlin, Virginie Dehame, Brigitte Dréno, Isabelle Gauvrit, Yannick Le Bris, Marc Grégoire, Soraya Saiagh, Sylvain Bercegeay, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de Thérapie Cellulaire et Génique [CHU Nantes] (UTCG), Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Service d'Hématologie Biologique [CHU Nantes], Laboratoire d'anatomie et cytologie pathologiques [CHU Nantes], Etablissement Français du Sang [Pays de la Loire] (EFS Pays de la Loire), EFS, Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: 030231 tropical medicine, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Vaccines, Dendritic cells, 03 medical and health sciences, 0302 clinical medicine, AML, [SDV.CAN] Life Sciences [q-bio]/Cancer, vaccine, Cadaver, Immunology and Allergy, Medicine, Humans, 030212 general & internal medicine, Adverse effect, Aged, Pharmacology, business.industry, Complete remission, Myeloid leukemia, apoptotic corpses, 3. Good health, Leukemia, Myeloid, Acute, Phase i ii, Apoptosis, Cancer research, Feasibility Studies, business, Research Paper
Abstract: This was a phase I/II study testing the feasibility of a vaccine by autologous leukemic apoptotic corpse-pulsed dendritic cells (DC) in elderly acute myeloid leukemia (AML) patients in first or second complete remission. Pulsed DC were administered at doses of 9 × 10(6) subcutaneously (1 mL) and 1 × 10(6) intra-dermally (0.1 mL). Five doses of vaccine were planned on days +1 + 7 + 14 + 21 and +35. Five DC-vaccines were produced and injected for all five patients included in the study. No severe adverse event was documented. Larger Phase 2 studies are now required to precise the role of DC-vaccines with leukemic apoptotic bodies in older as well as younger AML populations. (Clinicaltrials.gov NCT01146262)
Published: 2021
Full Text: View/download PDF

8. Comparison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft-versus-host-disease prophylaxis for matched unrelated donor transplant in acute myeloid leukemia. A study from the ALWP of the EBMT

Author: Bruno Lioure, Johan Maertens, Gérard Socié, Eric Deconinck, Annalisa Paviglianiti, Didier Blaise, Igor Wolfgang Blau, Claude Eric Bulabois, Mohamad Mohty, Anne Huynh, Pascal Turlure, Myriam Labopin, Arnon Nagler, Patrice Chevallier, Gaelle Guillerm, Patrice Ceballos, Edouard Forcade, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), Hôpital de Hautepierre [Strasbourg], Hôpital Lapeyronie [Montpellier] (CHU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), University Hospital Gasthuisberg [Leuven], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Tel Aviv University (TAU), NUNES, Jacques A, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Charité Campus Virchow-Klinikum (CVK), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Chaim Sheba Medical Center, Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], and Gestionnaire, HAL Sorbonne Université 5
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, Calcineurin Inhibitors, matched unrelated donor, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, acute myeloid leukemia, Gastroenterology, 03 medical and health sciences, Cyclosporine A, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Cumulative incidence, MMF, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, business.industry, mycophenolate mofetil, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Mycophenolic Acid, medicine.disease, CsA, 3. Good health, Fludarabine, Calcineurin, Leukemia, Leukemia, Myeloid, Acute, Graft-versus-host disease, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Unrelated Donors, Busulfan, 030215 immunology, medicine.drug
Abstract: International audience; The association of Cyclosporine A (CsA) and mycophenolate mofetil (MMF) has increased in the setting of reduced intensity conditioning (RIC). Nevertheless, the use of CsA or CsA+MMF has not been reported in a large and uniform cohort. We analyzed 497 patients with acute myeloid leukemia in complete remission (CR) who underwent matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). All patients received a fludarabine busulfan RIC regimen and anti-thymocyte globulin (ATG) with either CsA alone or in combination with MMF. The cumulative incidence (CI) of grade II-IV acute GvHD was 27% (95% CI 21-33%) for CsA and 33% (95% CI 27-38%) for CsA+MMF (p = 0.25). The 2-year CI of chronic GvHD was 38% (95% CI 31-45%) and 33% (95% CI 28-39%) for the CsA and the CsA+MMF group, respectively (p = 0.26). On multivariate analysis, no statistically significant differences with respect to relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD were found between the two groups, also when conducting a subgroup analysis in peripheral blood stem cells (PBSC) recipients. Our results support the importance of randomized trial to identify patients who could benefit from the addition of MMF in MUD HSCT.
Published: 2021
Full Text: View/download PDF

9. FLT3 ligand in acute myeloid leukemia: a simple test with deep implications

Author: Steven Knapper, Pierre Peterlin, Patrice Chevallier, Matthew Collin, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Cardiff University, Newcastle University [Newcastle], Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Cancer Research, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Intensive chemotherapy, acute myeloid leukemia, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, cytokine and chemokine biology, Medicine, Humans, FLT3 ligand, cytokine production and paraneoplastic conditions, Independent data, business.industry, Myeloid leukemia, Membrane Proteins, hemic and immune systems, Hematology, Prognosis, Hematopoiesis, Haematopoiesis, Leukemia, Myeloid, Acute, Cytokine, Oncology, fms-Like Tyrosine Kinase 3, Apoptosis, 030220 oncology & carcinogenesis, Tyrosine Kinase 3, embryonic structures, Mutation, Cancer research, Flt3 ligand, business, prognostication, 030215 immunology
Abstract: International audience; In contrast to Fms-like tyrosine kinase 3 (FLT3), the influence of FLT3 ligand (FLT3L) on acute myeloid leukemia (AML) biology and disease prognosis has been poorly described. Here we provide an overview of the role played by FLT3L in AML. While being a cytokine implicated in the regulation of hematopoiesis, both in normal situation and after intensive chemotherapy, FLT3L has also a role in enhancing proliferation, inhibiting apoptosis and conferring resistance to FLT3 inhibitors in AML. Moreover, recent independent data show how its measurement may be helpful in the disease management. Indeed, FLT3L could provide a low cost, rapid and noninvasive assessment of chemosensitivity and blast clearance that has robust prognostic significance for patients with AML.
Published: 2021
Full Text: View/download PDF

10. Early remodeling of the colonic mucosa after allogeneic hematopoietic stem cells transplantation: An open‐label controlled pilot study on 19 patients

Author: Anne Bessard, Grégoire David, Jérémy Brégeon, Patrice Chevallier, Michel Neunlist, Anne Jarry, Céline Bossard, Enrique Perez Cuadrado-Robles, Elise Esnaud, Emmanuel Coron, L Quénéhervé, The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire d'anatomie et cytologie pathologiques [CHU Nantes], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Male, medicine.medical_treatment, Graft vs Host Disease, Pilot Projects, Hematopoietic stem cell transplantation, Gastroenterology, immunology, confocal endomicroscopy, 0302 clinical medicine, immune system diseases, graft-versus-host disease, Prospective Studies, Intestinal Mucosa, 0303 health sciences, Hematopoietic Stem Cell Transplantation, Middle Aged, 3. Good health, digestive barrier, Cytokine, surgical procedures, operative, Oncology, 030220 oncology & carcinogenesis, Acute Disease, Cytokines, Female, Original Article, France, Stem cell, Adult, medicine.medical_specialty, Colon, graft‐versus‐host disease, Lumen (anatomy), Context (language use), chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Luminal, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, allogeneic hematopoietic stem cell transplantation, Aged, 030304 developmental biology, Intestinal permeability, business.industry, medicine.disease, Transplantation, Graft-versus-host disease, inflammation, endoscopic imaging, business
Abstract: International audience; Background: Graft-versus-host disease (GVHD), particularly acute digestive GVHD (aDGVHD), is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is necessary to identify predictive factors of GVHD to adapt prophylactic treatment.Objective: In this context, our pilot study aimed (i) to determine whether an early remodeling of the colonic mucosa occurred after allo-HSCT and (ii) to identify potential predictive mucosal markers of aDGVHD after allo-HSCT.Methods: Between day 21 and day 28 after the allo-HSCT, 19 allo-HSCT patients were included and had a rectosigmoidoscopy with probe-based confocal laser endomicroscopy (pCLE) recording and biopsies. Sixteen patients were included in the control group. Morphological (pCLE), functional (intestinal permeability), and inflammatory parameters (cytokine multiplex immunoassay) were assessed.Results: Among allo-HSCT patients, 11 patients developed GVHD, and 6 of them developed aDGVHD. Morphological and functional changes of the colonic mucosa occurred after allo-HSCT. Indeed, the perimeter of colonic crypts was significantly increased in allo-HSCT patients compared to controls as well as crypt lumen fluorescein leakage (53% vs. 9%), whereas crypts sphericity, roundness, Feret diameter, and mean vessel area were significantly decreased in allo-HSCT patients compared to the control group. In addition, interleukin-6 (IL-6), IL-33, and IL-15 levels in the supernatants of 24 h explant cultures of colonic biopsies were significantly increased in allo-HSCT patients compared to controls. Finally, there was no difference in pCLE parameters, intestinal permeability, and inflammatory cytokines between patients who developed aDGVHD and those who did not.Conclusion: This pilot study identified early colonic mucosa remodeling after allo-HSCT conditioning therapy, that is morphological and functional mucosal alterations as well as mucosal inflammation. As to whether these changes are first steps in GVHD initiation and could be considered as predictive biomarkers of aDGVHD need to be determined in a larger cohort of patients.
Published: 2021
Full Text: View/download PDF

11. Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT)

Author: José Rifón, Mohamad Mohty, David Beauvais, Dimitrios Karakasis, Emanuele Angelucci, Katya Mauff, Marie Robin, Jakob Passweg, Grzegorz Helbig, Luca Castagna, Tomasz Czerw, Liesbeth C. de Wreede, Jürgen Finke, Donal P. McLornan, Juan Carlos Hernández-Boluda, Nicola Polverelli, Péter Reményi, Martin Bornhäuser, Marie-Thérèse Rubio, Patrice Chevallier, Nicolaus Kröger, Dietrich W. Beelen, Ibrahim Yakoub-Agha, Tiarlan Sirait, Johan Maertens, Domenico Russo, Patrick Hayden, Radovan Vrhovac, Jean Baptiste Mear, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, spleen size, splenectomy, allogeneic hematopoietic cell transplantation, myelofibrosis, medicine.medical_treatment, Splenectomy, Medizin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Registries, Myelofibrosis, Busulfan, Melphalan, Survival rate, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Organ Size, Hematology, Middle Aged, Allografts, medicine.disease, Survival Rate, Transplantation, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Spleen, Vidarabine, Progressive disease, Follow-Up Studies, 030215 immunology
Abstract: The role of spleen size and splenectomy for the prediction of post-allogeneic hematopoietic stem cell transplant (allo-HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000-2017 after either fludarabine-busulfan or fludarabine-melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000-2009 vs 14.1% in 2010-2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44-0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01- 2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67-1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28-0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14- 0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87-2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.
Published: 2021
Full Text: View/download PDF

12. Interest of a third dose of BNT162b2 anti‐SARS‐CoV‐2 messenger RNA vaccine after allotransplant

Author: Philippe Moreau, Berthe-Marie Imbert, Thierry Guillaume, Steven Le Gouill, Marianne Coste-Burel, Thomas Gastinne, Amandine Le Bourgeois, Alice Garnier, Cyrille Touzeau, Maxime Jullien, Thomas Drumel, Nicolas Blin, Sophie Vantyghem, Benoit Tessoulin, Beatrice Mahe, Marie C. Béné, Anne Lok, Pierre Peterlin, Patrice Chevallier, Viviane Dubruille, Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Adult, Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.CAN]Life Sciences [q-bio]/Cancer, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) mRNA, Antibodies, Viral, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, vaccine, Correspondence, Medicine, Humans, Transplantation, Homologous, BNT162 Vaccine, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Messenger RNA, business.industry, SARS-CoV-2, COVID-19, allogeneic haematopoietic stem cell transplantation, Hematology, Organ Transplantation, Middle Aged, Allografts, Virology, Antibody Formation, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA, third dose, coronavirus disease 2019 (COVID-19), Female, BNT162b2, coronavirus disease 2019 (COVID‐19), business, Stem Cell Transplantation
Abstract: International audience; No abstract available
Published: 2021
Full Text: View/download PDF

13. Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort

Author: Patrice Chevallier, Alexis Caulier, Gabrielle Roth-Guepin, Xavier Thomas, Pierre-Yves Dumas, Yosr Hicheri, Florence Pasquier, Sarah Bertoli, Jean-Baptiste Micol, Edmond Chiche, Thomas Cluzeau, Ramy Rahmé, Arnaud Pigneux, Magalie Joris, Patrick Auberger, Pierre Peterlin, Caroline Lejeune, Ollivier Legrand, Mohamad Mohty, Norbert Vey, Caroline Bonmati, Lionel Ades, Michael Loschi, Christian Recher, Emmanuel Raffoux, Alexis Genthon, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., BMGIC, U1035 INSERM, University of Bordeaux, Bordeaux, France, Cellules souches hématopoïétiques et développement des hémopathies myéloïdes (CSHMyelo), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Saint-Eloi, CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'Hématologie, CHU Nice, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Hopital Saint-Louis [AP-HP] (AP-HP), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Lausanne (UNIL), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Institut Gustave Roussy (IGR), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Université Paris Cité (UPCité), and DESSAIVRE, Louise
Subjects: Adult, Oncology, medicine.medical_specialty, Multivariate analysis, Daunorubicin, [SDV]Life Sciences [q-bio], Internal medicine, hemic and lymphatic diseases, medicine, Humans, Aged, Retrospective Studies, Response rate (survey), Myeloid Neoplasia, business.industry, Cytarabine, Myeloid leukemia, Hematology, Minimal residual disease, Transplantation, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Cohort, business, medicine.drug
Abstract: CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD
Published: 2021
Full Text: View/download PDF

14. Diagnosis and prognosis are comforted by integrated assessment of next-generation sequencing in chronic myeloid malignancies. A real-life study

Author: Olivier Theisen, Pierre Peterlin, Viviane Dubruille, Patrice Chevallier, Pascal Godmer, Amandine Le Bourgeois, Sylvain Thepot, Anne Parcelier, Marion Loirat, Steven Le Gouill, Adrien Trebouet, Damien Luque Paz, Mélanie Mercier, S. Vigouroux, Mathilde Hunault, Céline Bossard, Marie C. Béné, Marion Eveillard, Audrey Ménard, Alice Garnier, Nadine Morineau, Camille Debord, Hervé Maisonneuve, François Subiger, Catherine Godon, Yannick Le Bris, Elsa Lestang, Jacques Delaunay, Sophie Vantyghem, Soraya Wuilleme, Anne Moreau, Ronan Le Calloch, Philippe Moreau, Lenaïg Le Clech, Thierry Guillaume, Bruno Villemagne, Valérie Ugo, Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département d'Hématologie Clinique [CHU d'Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Hématologie Biologique [CHU Nantes], Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Hôpital privé du Confluent [Nantes], Hématologie clinique [CH La Roche-sur-Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Laboratoire de Biologie [CHD Vendée, La Roche sur Yon], CHD Vendee (La Roche Sur Yon), Centre hospitalier de Saint-Nazaire, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Laboratoire d'Hématologie Biologique (Hémato - ANGERS), Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), Département de Pathologie [CHU Nantes], Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), and Bernardo, Elizabeth
Subjects: Oncology, medicine.medical_specialty, Myeloid, Somatic cell, diagnosis, theranostic, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Group B, DNA sequencing, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Neoplasms, medicine, Humans, 030304 developmental biology, 0303 health sciences, Myeloproliferative Disorders, business.industry, Myelodysplastic syndromes, Editorials, High-Throughput Nucleotide Sequencing, Hematology, Chronic Myeloproliferative Disorders, medicine.disease, Prognosis, somatic mutation by NGS, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Mutation, Bone marrow, business
Abstract: Next-generation sequencing (NGS) is used to investigate the presence of somatic mutations. The utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains unclear. We report the findings of an observational, multicenter study that aimed to assess the impact of somatic mutation testing by NGS in a reallife setting of chronic myeloid malignancies. A total of 177 patients were enrolled, partitioned into two overlapping groups. In group A (n=94), the indication was to search for clonal hematopoiesis, in a context of suspected myelodysplastic syndrome or myeloproliferative neoplasia. In group B (n=95), the theranostic impact of somatic mutations was studied. A panel of 34 genes was used on DNA extracted from blood or bone marrow samples. Within group A, the detection of clonal hematopoiesis supported the diagnosis of chronic myeloid malignancies for 31 patients while the absence of clonal hematopoiesis ruled out the suspected diagnosis in 47 patients. Within group B, NGS identified prognostically relevant somatic mutations in 32 patients, which had a therapeutic impact in 18 cases. By determining the presence or absence of somatic mutations, the application of NGS in daily practice was found to be useful for an integrated final diagnosis in 83% of the patients. Moreover, the search for somatic mutations had a prognostic impact that led to treatment modification in 19% of the cases. This study outlines the fact that adequate implementation of new investigations may have a significant positive medico-economic impact by enabling appropriate management of patients.
Published: 2021
Full Text: View/download PDF

15. Splenectomy before allogeneic hematopoietic cell transplantation for myelofibrosis: A French nationwide study

Author: Jean-Baptiste Bossard, Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Mohamad Mohty, Florence Beckerich, Marie-Thérèse Rubio, Patrice Chevallier, Jérôme Cornillon, Fiorenza Barraco, Federico Garnier, Marie Robin, Alain Duhamel, Gandhi Damaj, Corentin Orvain, Jean-Baptiste Beuscart, Ibrahim Yakoub-Agha, Mathieu Meunier, Thomas Cluzeau, Amandine Charbonnier, Patrice Ceballos, Didier Blaise, Carmen Botella-Garcia, Jean-Jacques Kiladjian, Jacques-Olivier Bay, Tony Marchand, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Splenectomy, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Registries, Myelofibrosis, Survival rate, ComputingMilieux_MISCELLANEOUS, business.industry, Incidence (epidemiology), Hazard ratio, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Allografts, medicine.disease, 3. Good health, Surgery, Survival Rate, Transplantation, surgical procedures, operative, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Female, France, business, 030215 immunology
Abstract: The value of pretransplant splenectomy in patients with myelofibrosis (MF) is subject to debate, since the procedure may preclude subsequent allogeneic hematopoietic cell transplantation (allo-HCT). To determine the impact of pretransplant splenectomy on the incidence of allo-HCT, we conducted a comprehensive retrospective study of all patients with MF for whom an unrelated donor search had been initiated via the French bone marrow transplantation registry (RFGM) between 1 January 2008 and 1 January 2017. Additional data were collected from the patients' medical files and a database held by the French-Language Society for Bone Marrow Transplantation and Cell Therapy (SFGM-TC). We used a multistate model with four states ("RFGM registration"; "splenectomy"; "death before allo-HCT", and "allo-HCT") to evaluate the association between splenectomy and the incidence of allo-HCT. The study included 530 patients from 57 centers. With a median follow-up time of 6 years, we observed 81 splenectomies, 99 deaths before allo-HCT (90 without splenectomy and nine after), and 333 allo-HCTs (268 without splenectomy and 65 after). In a bivariable analysis, the hazard ratio [95% confidence interval (CI)] for the association of splenectomy with allo-HCT was 7.2 [5.1-10.3] in the first 4 months and 1.18 [0.69-2.03] thereafter. The hazard ratio [95% CI] for death associated with splenectomy was 1.58 [0.79-3.14]. These reassuring results suggest that splenectomy does not preclude allo-HCT in patients with MF.
Published: 2021
Full Text: View/download PDF

16. Scoring system for clinically significant CMV infection in seropositive recipients following allogenic hematopoietic cell transplant: an SFGM-TC study

Author: Xavier Poiré, Didier Blaise, Patrice Ceballos, Elodie Drumez, Anne Uyttebroeck, Hélène Labussière, Anne Huynh, Thomas Cluzeau, Marie-Thérèse Rubio, Patrice Chevallier, Stéphanie Nguyen, Eric Deconinck, Eolia Brissot, Régis Peffault de Latour, Alain Duhamel, David Beauvais, Anne Thiebaut, Edouard Forcade, Ibrahim Yakoub-Agha, Sébastien Maury, Jean-Henri Bourhis, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Department of Oncology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire [Grenoble] (CHU), Cliniques universitaires St Luc [Bruxelles], CHU Henri Mondor, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Saint-Antoine [AP-HP], Réseau régional de cancérologie Onco-Occitanie, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: medicine.medical_specialty, Transplantation Conditioning, Congenital cytomegalovirus infection, Cytomegalovirus, Viremia, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human leukocyte antigen, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Transplantation, Hematopoietic cell, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Total body irradiation, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Cytomegalovirus Infections, business, 030215 immunology
Abstract: In order to identify cytomegalovirus (CMV)-seropositive patients who are at risk of developing CMV infection following first allogeneic hematopoietic cell transplantation (allo-HCT), we built up a scoring system based on patient/donor characteristics and transplantation modalities. To this end, 3690 consecutive patients were chronologically divided into a derivation cohort (2010-2012, n = 2180) and a validation cohort (2013-2014, n = 1490). Haploidentical donors were excluded. The incidence of first clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) at 1, 3, and 6 months in the derivation cohort was 13.8%, 38.5%, and 39.6%, respectively. CMV-seropositive donor, unrelated donor (HLA matched 10/10 or HLA mismatched 9/10), myeloablative conditioning, total body irradiation, antithymocyte globulin, and mycophenolate mofetil significantly and independently affected the incidence of 3-month infection. These six factors were selected to build up the prognostic model. Four risk groups were defined: low, intermediate-low, intermediate-high, and high-risk categories, with a 3-month predicted incidence of first clinically significant CMV infection in the derivation cohort of 22.2%, 31.1%, 45.4%, and 56.9%, respectively. This score represents a framework for the evaluation of patients who are at risk of developing clinically significant CMV infection following allo-HCT. Prospective studies using this score may be of benefit in assessing the value of anti-CMV prophylaxis in well-defined patient cohorts.
Published: 2020
Full Text: View/download PDF

17. Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia

Author: Amandine Lebourgeois, Gaëlle David, Béatrice Clémenceau, Thierry Guillaume, Katia Gagne, Ketevan Gendzekhadze, Patrice Chevallier, Catherine Willem, Pierre Peterlin, Léa Dubreuil, Marie C. Béné, Dhon Roméo Makanga, Alice Garnier, Anne Cesbron, Christelle Retière, Francesca Da Rin de Lorenzo, Nolwenn Legrand, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Etablissement Français du Sang [Nantes], Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), City of Hope National Medical Center, LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_treatment, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human leukocyte antigen, Biology, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Cytotoxic T cell, acute leukemia, Receptor, Acute leukemia, natural killer cells, repertoire, CMV, Myeloid leukemia, Hematopoietic stem cell, Immunotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, KIR, HLA, 030104 developmental biology, medicine.anatomical_structure, Oncology, Immunology, 030215 immunology
Abstract: International audience; Natural killer (NK) cells are key cytotoxic effectors against malignant cells. Polygenic and polymorphic Killer cell Immunoglobulin-like Receptor (KIR) and HLA genes participate in the structural and functional formation of the NK cell repertoire. In this study, we extensively investigated the anti-leukemic potential of NK cell subsets, taking into account these genetic parameters and cytomegalovirus (CMV) status. Hierarchical clustering analysis of NK cell subsets based on NKG2A, KIR, CD57 and NKG2C markers from 68 blood donors identified donor clusters characterized by a specific phenotypic NK cell repertoire linked to a particular immunogenetic KIR and HLA profile and CMV status. On the functional side, acute lymphoblastic leukemia (ALL) was better recognized by NK cells than acute myeloid leukemia (AML). However, a broad inter-individual disparity of NK cell responses exists against the same leukemic target, highlighting bad and good NK responders. The most effective NK cell subsets against different ALLs expressed NKG2A and represented the most frequent subset in the NK cell repertoire. In contrast, minority CD57+ or/and KIR+ NK cell subsets were more efficient against AML. Overall, our data may help to optimize the selection of hematopoietic stem cell donors on the basis of immunogenetic KIR/HLA for ALL patients and identify the best NK cell candidates in immunotherapy for AML.
Published: 2020
Full Text: View/download PDF

18. Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor

Author: Evelyne Marry, Catherine Faucher, Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Mohamad Mohty, Patrice Chevallier, Clémence Deteix, Alison M. Foote, Noel Milpied, Fabrice Larosa, Sabine Furst, Frédéric Garban, Ibrahim Yakoub-Agha, Anne Huynh, Sylvain Chantepie, Jean-Yves Cahn, Jacques-Olivier Bay, Régis Peffault de Latour, Nathalie Fegueux, Florence Mesnil, Hélène Labussière Wallet, Françoise Audat, Jean-Henri Bourhis, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Umbilical cord, 03 medical and health sciences, 0302 clinical medicine, Unrelated Donor, Internal medicine, medicine, Humans, Transplantation, Homologous, Sibling, Alternative donor, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, business.industry, Siblings, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 3. Good health, Leukemia, Myeloid, Acute, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Stem cell, business, Unrelated Donors, 030215 immunology
Abstract: Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for high-risk acute myeloid leukemia. In the absence of an HLA-matched related or unrelated donor (MRD or MUD), the best alternative donor source remains controversial. Umbilical cord blood and haploidentical donors offer a time advantage when considering the duration from treatment indication to transplantation. This retrospective multicenter study of a French registry compares overall survival for alternative donor transplants in the 18 months following decision to transplant in the absence of a MRD between four groups of transplanted patients: MUD (control); HLA-mismatched MUD (mMUD); umbilical cord blood (UCB); and haploidentical (haplo). Between March 2012 and July 2016, 1302 patients were transplanted with MUD (n=803), mMUD (n=219), UCB (n=153) and haplo (n=127) donors. Multivariate analyses were conducted for overall survival 18 months after registration, overall survival after transplant, and transplant-related mortality, with adjustment for the several variables. After adjustment, the type of donor did not influence any of the three endpoints. Our results confirmed the significant negative impact of a longer time interval between registration and transplant: HR=1.04 [1.02–1.06] (p
Published: 2020
Full Text: View/download PDF

19. Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation

Author: Sylvain Chantepie, Cécile Fourrage, Françoise Huguet, Patrice Chevallier, Elizabeth Macintyre, Hervé Dombret, Nicolas Boissel, Emmanuelle Tavernier, Véronique Lhéritier, Stéphane Leprêtre, Loïc Passini, Vahid Asnafi, Sébastien Maury, Martine Escoffre, Carlos Graux, Ludovic Lhermitte, Emmanuel Raffoux, Patrick Villarese, Norbert Ifrah, Yves Chalandon, Thibaut Leguay, Thorsten Braun, Xavier Thomas, Mathilde Hunault, Rathana Kim, Florian Thonier, Aurore Touzart, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Service d'hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie adulte [Hôpital de Saint Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Plateforme de Bioinformatique [Paris] (Fondation Imagine), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Groupe de recherche sur la leucémie lymphoblastique aiguë chez l'adulte [Lyon] (CHU HCL - CHLS), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Laboratoire d’Hématologie [CHU Henri-Mondor - APHP], CHU Henri Mondor, CHU Pontchaillou [Rennes], Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Genève = University of Geneva (UNIGE), Swiss Group for Clinical Cancer Research [Bern, Switzerland], CHU Dinant-Godinne UCL Namur [Yvoir, Belgique], We thank the Swiss State Secretariat for Education, Research and Innovation (SERI) Switzerland for support. We thank Force Hemato and Association pour la Recherche contre le Cancer (ARC) for support., Bernardo, Elizabeth, Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hematologie [CHU Pontchaillou, Rennes] (Pôle de Biologie), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], University of Geneva [Switzerland], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Neoplasm, Residual, medicine.medical_treatment, Hematopoietic stem cell transplantation, medicine.disease_cause, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, 0302 clinical medicine, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics/pathology/therapy, Receptors, Hematopoietic Stem Cell Transplantation/mortality, ddc:616, Mutation, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Survival Rate, 030220 oncology & carcinogenesis, Tumor/genetics, Residual/genetics/pathology/therapy, Female, Stem cell, Adult, Homologous, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Transplantation, Homologous, Humans, Clinical significance, Interleukin-7 receptor, Chemotherapy, Neoplastic, Transplantation, Receptors, Interleukin-7, business.industry, Minimal residual disease, 030104 developmental biology, Gene Expression Regulation, Interleukin-7/genetics, Neoplasm, business, Biomarkers, Follow-Up Studies
Abstract: International audience; The prognostic value of IL7-receptor pathway (IL7Rp) mutations in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. We performed a comprehensive study of 200 adult patients with TALL included in the GRAALL2003/2005 protocols to address the clinical significance of IL7Rp mutations. Next-generation sequencing of the IL7Rp (IL7R/JAK1/ JAK3/STAT5B) revealed that IL7Rp mutations were frequent in adult TALL (28%) particularly in immature/early T-cell progenitor (ETP)-ALL. They were associated with mutations of NOTCH-pathway, PHF6, and PRC2 components but not with K/NRAS. IL7Rp mutated (IL7Rp mut) TALL were slow-responders, with a high rate of M2/M3 day-8 marrow compared with IL7Rp non-mutated (IL7Rp WT) TALL (p = 0.002) and minimal residual disease positivity at 6-weeks (MRD1) (p = 0.008) but no difference in MRD2 positivity at 12-weeks. Despite this, no adverse prognosis was evidenced when censored for allogeneic hematopoietic stem cell transplantation (HSCT). In time-dependent analysis, HSCT did not benefit IL7Rp mut patients whereas it was of marked benefit to IL7Rp WT cases. IL7Rp-mutations identify a subgroup of slow-responder T-ALLs which benefit from post-induction chemotherapy regimens but not from HSCT. Our data suggest that prior knowledge of the mutation status of IL7Rp may influence HSCT decision and help to guide therapy reduction.
Published: 2020
Full Text: View/download PDF

20. [Haploidentical hematopoietic stem cell transplant: How to choose the best donor? Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]

Author: Bénédicte Bruno, C. Giannoli, Valérie Dubois, Stéphanie Nguyen, Pascale Loiseau, Raynier Devillier, Paul-Olivier Rouzaire, Patrice Chevallier, Ibrahim Yakoub-Agha, Kahina Amokrane, Mhamed Harif, Gwendaline Guidicelli, Florent Delbos, Yves Beguin, Pauline Varlet, CCSD, Accord Elsevier, Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie, Université de Liège, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], Etablissement Français du Sang [Nantes], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement français du sang- Rhône-Alpes [Lyon], Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Lille (CHU de Lille), Department of Microbiology and Immunology, East Carolina University [Greenville] (ECU), and University of North Carolina System (UNC)-University of North Carolina System (UNC)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Myeloid, Haploidentical transplantation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Human leukocyte antigen, Hematopoietic stem cell transplantation, DSA, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Donor choice, medicine, Radiology, Nuclear Medicine and imaging, Greffe haplo-identique, 10. No inequality, Gynecology, business.industry, Hematology, General Medicine, medicine.disease, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], Specific antibody, 030104 developmental biology, medicine.anatomical_structure, Oncology, Bone transplantation, 030220 oncology & carcinogenesis, Choix du donneur, Bone marrow, Stem cell, business
Abstract: International audience; Haploidentical hematopoietic stem cell transplantation has been growing steadily since 2012. The SFGM-TC has twice published guidelines concerning T-cell repleted haploidentical grafts with high dose cyclophosphamide post-transplantation. The 2013 workshop recommended using the non-myeloablative Baltimore protocol with bone marrow and developed prospective protocols to evaluate these transplantations. The 2015 workshop reported improved results of reduced conditioning regimens in Hodgkin's lymphoma and intensive conditioning in myeloid hemopathies, and a similar outcome with 10/10 HLA matched donor with the same disease-risk score thus raising the question of the qualifier "alternative" for haploidentical transplants. The current work concerns the criteria for selecting the donor. The main criterion remains the absence of anti-HLA antibodies directed against the donor present in the recipient sera (DSA - Donor Specific Antibodies). In case of DSA and in the absence of an alternative donor, desensitization protocols exist. The other criteria are impossible to prioritize: age, sex, CMV, and blood type. The degree of relatedness and the number of HLA incompatibilities do not seem to be a criterion of choice. The 'ideal' donor would be a young man, CMV-matched, without major ABO incompatibility with a marrow transplant. There is insufficient data for the KIR-ligand and NIMA/NIPA mismatch. Peripheral stem cell grafts appear to yield more acute GVHD than bone marrow grafts after intensive conditioning, but with comparable survival rates. Based on the literature review, the comparison of haploidentical with unrelated donors encourages inclusion in existing national protocols randomizing these different donors.
Published: 2020
Full Text: View/download PDF

21. Progression of disease within 2 years (POD24) is a clinically relevant endpoint to identify high-risk follicular lymphoma patients in real life

Author: Amandine Le Bourgeois, Patrice Chevallier, Philippe Moreau, Christophe Leux, Benoit Tessoulin, Steven Le Gouill, Thierry Guillaume, Beatrice Mahe, Clara Sortais, Cyrille Touzeau, Thomas Gastinne, Anne Moreau, Anne Lok, Alice Garnier, Pierre Peterlin, Viviane Dubruille, Nicolas Blin, Céline Bossard, Bernardo, Elizabeth, Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d’Anatomopathologie [CHU Nantes], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Département de l'Information Médicale [CHU Nantes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Male, Oncology, Time Factors, Follicular lymphoma, Cohort Studies, 0302 clinical medicine, Recurrence, Risk Factors, Prednisone, Antineoplastic Combined Chemotherapy Protocols, Lymphoma, Follicular, Aged, 80 and over, Hematology, General Medicine, Middle Aged, Prognosis, 3. Good health, Treatment Outcome, Vincristine, 030220 oncology & carcinogenesis, Cohort, Disease Progression, Female, Rituximab, France, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, medicine, Humans, Aged, Retrospective Studies, business.industry, medicine.disease, Survival Analysis, Lymphoma, Clinical trial, Doxorubicin, Neoplasm Grading, business, 030215 immunology
Abstract: International audience; Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma with heterogeneous outcomes. Progression or relapse of FL within 2 years (so-called POD24) after diagnosis is associated with a poor outcome for patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) in clinical trials. POD24 needs further validation before it can be used as a relevant endpoint to assess treatment efficacy. In the present retrospective monocentric study, we investigated the predictive value of POD24 in a cohort of grade 1, 2, or 3a FL patients treated in our institution (Nantes Medical University, France) and registered in our local database. We investigated the nature of treatment lines, patients' outcomes, and the prognostic value of POD24. Between 2007 and 2016, 317 patients were included. After first-line therapy, 60 patients relapsed within 2 years (POD24-pos cohort), and 254 patients did not relapse within 2 years (PO24-neg cohort). Thirty-three patients died, and 34 patients had an aggressive transformation. The median follow-up is 59.9 months (1.6-395.5). The median PFS is 59.9 months. Overall survival (OS) at 1 year, 3 years, and 5 years is 98.4% [97.0-99.8], 95.1% [92.6-97.6], and 92.5% [89.3-95.9], respectively. The 5-year OS was statistically lower for POD24-pos patients (82% [71.9-93.5]) than for POD24-neg patients (93.3% [88.98-97.8]) (p = 10-5). In multivariate analyses, transformation was predictive of OS, and PS (≥ 1) was predictive of POD24. POD24 is predictive of a worse OS and may be recommended as a relevant endpoint in clinical trials and in real life in particular for patients with advanced disease.
Published: 2020
Full Text: View/download PDF

22. Autologous and Allogeneic Hematopoietic Stem-Cell Transplantation for Patients with Richter's Syndrome: A Large Series from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Author: Didier Blaise, Michel van Gelder, Gwendolyn Van Gorkom, Mark Ringhoffer, Henrik Sengeloev, Xavier Poiré, Martin Gramatzki, Olivier Tournilhac, Romain Guieze, Dirk-Jan Eikema, Patrice Chevallier, Jenny Byrne, Bendt Nielsen, Emmanouil Nikolousis, Liesbeth C. de Wreede, Patrick Hayden, Jürgen Finke, Jakob Passweg, Nienke Zinger, Nicola Mordini, Ibrahim Yakoub-Agha, Jan J. Cornelissen, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHADEYRON, DOMINIQUE
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Chronic lymphocytic leukemia, medicine.medical_treatment, Immunology, Allopurinol, Hematopoietic stem cell transplantation, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Large series, Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Transplantation, Graft-versus-host disease, Stem cell, business, 030215 immunology, medicine.drug
Abstract: Introduction. Chronic lymphocytic leukemia (CLL) has typically an indolent course but can undergo transformation into a more aggressive lymphoma so called Richter's syndrome. While the advent of novel targeted therapies is transforming the management of patients with CLL, these drugs failed to prevent the risk of RS. RS is associated with a very poor outcome and is thus becoming the main obstacle to long term CLL control. Autologous (auto-) and allogeneic (allo-) hematopoietic stem-cell transplantation (-SCT) have been recommended as the treatment of choice in eligible patients with clonally related RS (Rossi Blood 2018) but previous experience is still limited to less than 50 cases. We here aimed to investigate the safety and efficacy of both auto- and allo-SCT for patients with RS in a large cohort in a period overlapping the advent of novel agents. Methods. We report on a retrospective study of consecutive adult patients with RS who underwent auto- or allo-SCT between 2008 and 2018 in EBMT centers. Results. A total of 197 patients (M/F= 133/64) were included in the present study; 125 patients received allo-SCT and 72 auto-SCT. The main difference between these 2 cohorts was the median age at transplant that was lower in the allo- than in the auto-SCT group (median age 57 [18-71] vs 61 [39-74] years, p = 0.006). Regarding the allo-SCT cohort, median time from RS diagnosis to SCT was 10 months [1.1-322.8] and 54.2% had received >2 therapeutic lines for RS. At allo-SCT, 60 (48.4%) were in CR and 53 (42.7%) in PR or SD. Most patients received reduced intensity conditioning (RIC) regimen (n= 90, 72.6%) and peripheral blood (89.6%) as stem cell source. Donors were related (matched, n=40 (33%) or mismatched, n=4 (3%)) or unrelated (matched, n= 76 (61%) and mismatched, n=4 (3%). A total of 41 patients (33.6%) received total body irradiation (TBI). With a median follow-up of 48 months, 2-year OS was 46% (36-55%) and 2-year PFS 38% (28-48%). Two-year cumulative incidence of relapse (CIR) was 31% (22-40%) as was the 2-year NRM (Figure 1). Two-year CIR was significantly reduced in patients with ≤2 therapeutic lines for RS (12% (1-22%) vs 41% (26-55%); p=0.005). Performance status affected 2-y PFS (24% (7-42%) if Karnofsky index Regarding the auto-HSCT cohort, median time from RS diagnosis to HSCT was 7.8 months [2.6-102.7] and 66.7% had received >2 lines for RS. At auto-SCT, 36 (52.2%) were in CR and 36 (37.7%) in PR or SD. With a median follow-up of 18 months, 2-year OS was 69 % (56-82%) and 2-year PFS 47% (33-62%). Two-year cumulative incidence of relapse (CIR) was 46% (32-60%) and 2-year NRM was 7% (0-13%) (Figure 2). CR patients presented better PFS (69% (50-88%) vs 29% (9-50%); p=0.002) and OS (82% (66-97%) vs 56% (35-78%) ; p=0.03). Performance status affected 2-y PFS (25% (2-48%) if Karnofsky index 90%, p = 0.005) and 2-y OS (55% (29-82%) if Karnofsky index 90%, p = 0.04). Disclosures Guièze: Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria; Abbvie: Honoraria. Byrne:Ariad/Incyte: Honoraria, Speakers Bureau. Finke:Riemser: Honoraria, Other: research support, Speakers Bureau; Neovii: Honoraria, Other: research support, Speakers Bureau; Medac: Honoraria, Other: research support, Speakers Bureau. Chevallier:Incyte: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Daiichi Sankyo: Honoraria.
Published: 2019

23. Donor selection for a second allogeneic stem cell transplantation in AML patients relapsing after a first transplant: a study of the Acute Leukemia Working Party of EBMT

Author: Avichai Shimoni, Myriam Labopin, Friedrich Stoelzel, Patrice Chevallier, Martin Gramatzki, Ernst Holler, Nicolaus Kröger, Mohamad Mohty, Matthias Stelljes, Didier Blaise, Arnon Nagler, Eric Deconinck, Fabio Ciceri, Jürgen Finke, Nathalie Fegueux, Tel Aviv University [Tel Aviv], University Hospital Freiburg, IRCCS San Raffaele Scientific Institute [Milan, Italie], Hôpital JeanMinjoz, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Westfälische Wilhelms-Universität Münster (WWU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospital Regensburg, Hôpital Lapeyronie [Montpellier] (CHU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Shimoni, A., Labopin, M., Finke, J., Ciceri, F., Deconinck, E., Kroger, N., Gramatzki, M., Stelljes, M., Blaise, D., Stoelzel, F., Chevallier, P., Holler, E., Fegueux, N., Mohty, M., and Nagler, A.
Subjects: Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Myeloid, [SDV]Life Sciences [q-bio], Graft vs Host Disease, lcsh:RC254-282, Article, Acute myeloid leukaemia, Donor Selection, Young Adult, 03 medical and health sciences, Medical research, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Transplantation, Homologous, Young adult, Aged, Acute leukemia, Donor selection, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Transplantation, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Retreatment, Female, business, 030215 immunology
Abstract: Second allogeneic stem-cell transplantation (SCT2) is a therapeutic option for patients with AML relapsing after a first transplant. Prior studies have shown similar results after SCT2 from the same or different donor; however, there are limited data on second non-T-depleted haplo-identical transplant in this setting. We retrospectively analyzed SCT2 outcomes in 556 patients, median age 46 years, relapsing after first transplant given in CR1. Patients were divided into three groups based on SCT2 donor (donor2): same donor (n = 163, sib/sib-112, UD/UD-51), different matched donor (n = 305, sib/different sib-44, sib/UD-93, UD/different UD-168), or haplo-donor (n = 88, sib/haplo-45, UD/haplo-43). Two-year leukemia-free survival (LFS) rate after SCT2 was 23.5%, 23.7%, and 21.8%, respectively (P = 0.30). Multivariate analysis showed no effect of donor2 type on relapse: hazard ratio (HR) 0.89 (P = 0.57) and 1.11 (P = 0.68) for different donor and haplo-donor compared to same donor, respectively. However, donor2 did predict for non-relapse mortality (NRM) after SCT2: HR 1.21 (P = 0.50) and 2.08 (P = 0.03), respectively, and for LFS: HR 1.00 (P = 0.97) and 1.43 (P = 0.07), respectively. In conclusion, SCT2 with the same or different matched donor is associated with similar outcomes in patients with relapsed AML. Non-T-depleted haplo-identical transplant may be associated with higher NRM, similar relapse rate and with no better results in this setting.
Published: 2019
Full Text: View/download PDF

24. Prospective phase II study of prophylactic low-dose azacitidine and donor lymphocyte infusions following allogeneic hematopoietic stem cell transplantation for high-risk acute myeloid leukemia and myelodysplastic syndrome

Author: Myriam Labopin, Philippe Moreau, Thierry Guillaume, Noel Milpied, Leonardo Magro, Pierre Peterlin, Florent Malard, Cécile Borel, Marie-Thérèse Rubio, Stephane Vigouroux, Patrice Chevallier, Reza Tabrizi, Mohamad Mohty, Ibrahim Yakoub-Agha, Alice Garnier, Béatrice Gaugler, Anne Huynh, Centre hospitalier universitaire de Nantes (CHU Nantes), Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Bordeaux [Bordeaux], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Azacitidine, Graft vs Host Disease, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Relapse prevention, Gastroenterology, Disease-Free Survival, Donor lymphocyte infusion, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Cumulative incidence, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, Cause of death, Transplantation, business.industry, Incidence, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, Allografts, 3. Good health, Survival Rate, Leukemia, Myeloid, Acute, Lymphocyte Transfusion, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Female, Unrelated Donors, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract: Thirty patients, with high-risk acute myeloid leukemia (AML, n = 20) or myelodysplastic syndrome (MDS, n = 10), were enrolled in a phase II trial entailing prophylactic post-transplant azacitidine (AZA) plus escalated doses of donor lymphocyte infusion (DLI). The median number of AZA cycles was 5 (1-12) with 10 patients (33%) completing the 12 projected cycles. DLI were performed in 17 patients: 5 received one DLI, 2 received 2 DLI and 8 received 3 infusions. AZA was well tolerated, but discontinued in 20 patients primarily due to graft-versus-host disease (GvHD) and relapse. The cumulative incidence (CI) of grade 1-3 acute GvHD was 31.5% and the chronic GvHD CI was 53% at 2 years. At a median follow-up of 49 months (27-63), 18 patients are alive. The overall and disease-free survivals are 65.5% (CI 95% = 48.2-82.8) at 2 years. Cause of death was mainly relapse for 9 patients. The median time to relapse was 7 months (2.5-58) and the cumulative incidence of relapse at 2 years was 27.6% (CI 95% = 12.8-44.6). These results confirm that AZA is well tolerated as a prophylactic treatment to reduce the risk of post-transplantation relapse and compared favorably to those of patients who receive no post-transplant maintenance.
Published: 2019
Full Text: View/download PDF

25. Complications pulmonaires post-greffe : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Nimrod Buchbinder, Elodie Lhuillier, Bouamama Farah, Yosr Hicheri, Patrice Chevallier, Jérôme Cornillon, Leonardo Magro, Remy Dulery, Eolia Brissot, Laure Vincent, Ibrahim Yakoub-Agha, Frédéric Wallyn, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Thrombotic microangiopathy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, Lung biopsy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Stage (cooking), medicine.diagnostic_test, business.industry, Interstitial lung disease, Hematology, General Medicine, medicine.disease, 3. Good health, 030104 developmental biology, Bronchoalveolar lavage, Oncology, 030220 oncology & carcinogenesis, Etiology, business, Cryptogenic Organizing Pneumonia
Abstract: Pulmonary complications after allogeneic hematopoietic stem cell transplantation occur frequently (30-75%), vary in severity, and sometimes prove lethal. They may occur at an early stage post-transplant before D100 but may also surface later. Etiological support for these complications has shown a beneficial impact on survival. When faced with early complications, non-invasive tests, scans, and microbiological tests must be rapidly implemented. In the majority of cases, these tests facilitate diagnosis. In cases where microbiological non-invasive tests are negative, and the patient shows a steady respiratory condition, bronchoalveolar lavage can be effective if it is implemented in the first four days following the onset of pulmonary symptoms. This diagnostic approach should in no way occlude the introduction of broad-spectrum antibiotics in these profoundly immunocompromised patients. Later pulmonary complications are the most often not infectious. They include different anatomo-clinical conditions: cryptogenic organizing pneumonia; interstitial lung disease; idiopathic pleuroparenchymal fibroelastosis. Vascular disorders may include hypertension, thrombotic microangiopathy, venous thromboembolism, and pleural effusions. These conditions must be monitored using RFE (respiratory functional exploration) which allows early detection and therapeutic intervention. A combination of RFE and thoracic radiology scans will provide diagnostic assessment. Bronchoalveolar lavage is indicated when an infection is suspected or before systemic corticosteroid therapy. A lung biopsy should be discussed on a case-by-case basis, such as in cases of interstitial pulmonary disorders.
Published: 2019
Full Text: View/download PDF

26. CPX-351 Induces Deep Response and Suppress the Impact of Poor Prognosis Mutations (TP53, ASXL1, RUNX1 and EVI1) Defined By ELN-2017 in t-AML and MRC AML: A Report from a Multicentric French Cohort

Author: Xavier Thomas, Alexis Genthon, Thomas Cluzeau, Mathieu Sauvezie, Edmond Chiche, Gabrielle Roth Guepin, Caroline Bonmati, Christian Recher, Ramy Rahmé, Patrice Chevallier, Florence Pasquier, Patrick Auberger, Lionel Ades, Michael Loschi, Mohamad Mohty, Arnaud Pigneux, Olivier Legrand, Emmanuel Raffoux, Pierre Peterlin, Caroline Lejeune, Alexis Caulier, Magalie Joris, Sarah Bertoli, Jean Baptiste Micol, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Hôpital Hôtel-Dieu [Nantes] (Centre Hospitalier Universitaire de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), DESSAIVRE, Louise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Service d'Hématologie, CHU Nice, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Physique de Nice (INPHYNI), Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Picardie Jules Verne (UPJV), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lausanne (UNIL), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), XLIM (XLIM), and Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, medicine.medical_specialty, Daunorubicin, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Hematopoietic stem cell transplantation, medicine.disease_cause, Biochemistry, chemistry.chemical_compound, Internal medicine, hemic and lymphatic diseases, medicine, Mutation, Therapy related, business.industry, Cell Biology, Hematology, medicine.disease, [SDV] Life Sciences [q-bio], RUNX1, chemistry, Cohort, Cytarabine, business, Febrile neutropenia, medicine.drug
Abstract: Introduction CPX-351 is a liposomal formulation of cytarabine and daunorubicin packaged at a 5:1 molar ratio. This drug has recently been approved by FDA and EMEA for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). The primary objective of this study was to analyze the efficacy of CPX-351 in a real-life setting, evaluating the impact of mutations on response and minimal residual disease (MRD) in responding patients. Methods We retrospectively collected data from patients treated by CPX-351 in eleven centers in France. Clinical, biological and treatment information were available for all patients. NGS (19 genes or more) was performed in 67 patients (84%) at diagnosis. Overall response rate (ORR) was defined by complete remission (CR) and CR with incomplete haematological recovery (CRi). Among the patients in CR or CRi, 25 (56%) had MRD evaluation assessed by NGS or flow cytometry. Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics). Results Between April 2018 and July 2019, 80 patients treated with CPX-351 were included in this study. Sex ratio M/F was 43/37 and median age was 66 years old (range 20-83). AML subtypes were MRC-AML (61%) including AML with prior myelodysplastic syndrome (MDS-AML) (33%), prior chronic myelomonocytic leukemia (CMML-AML) (7%), or t-AML (29%). Sixteen patients (20%) had received prior treatment by hypomethylating agents (HMA), at the time of MDS diagnosis, before AML evolution. According to ELN 2017 classification, genetic risk was favorable, intermediate and adverse in 1 (1%), 31 (38%) and 47 (58%), respectively. 36% and 28% patients had complex and monosomal karyotypes, respectively. Assessed by NGS the most frequent mutated gene were : RUNX1 (n=17, 25%), TP53 (n=15, 22%), ASXL1 (n=14, 21%), TET2 (n=13, 19%), DNMT3A (n=11, 16%), srsf2 (n=9, 13%), FLT3-ITD (n=8, 12%), CBL (n=7, 10%), WT1 (n=7, 10%), and EZH2 (n=7, 10%). According to a genetic ontogeny-based classifier (Lindsley et al., Blood 2015), 23 patients (34%), 29 (43%), 15 (22%) had de novo/pan-AML, secondary type mutations AML, and TP53 mutated AML, respectively. Only 4 patients discontinuing treatment due to prolonged haematological toxicity. Early death rate was 5% and 8.75% through day 30 and day 60, respectively. Median time to neutrophil recovery (>0,5 G/L) and platelet recovery (>20G/L) after induction was 29 days (range 19-78) and 28 days (range 12-77), respectively. Seventy-five patients (95%) had at least one grade 3 or more AEs, including 69 (86%) febrile neutropenia. We observed gastrointestinal toxicity 32 patients (40%) (nausea/vomiting (30%/11%), mucositis (15%)) including 4% with grade 3 or more and alopecia in only 12%. ORR was 45/80 (56%) after induction 1 including 53% CR and 3% CRi. ORR increased to 58% after induction 2. Among the 45 CR/CRi patients, 25 were evaluable for MRD at the time of the 1st consolidation. 72% had MRD below 10-3 (64% below 10-4). Prior treatment by HMA and presence of monosomal karyotype were identified as factors predicting a lower rate of CR/CRi (P=0.001 and P=0.002, respectively). Lindsley's classifier predicted significantly a better chemosensitivity in de novo/pan-AML mutations (P= 0.037). Poor molecular prognosis subgroups defined by 2017 ELN risk stratification (n = 53) as TP53, ASXL1, RUNX1 and EVI1 mutations were not associated with a lower response rate with CPX-351 (Table 1). Twenty-one (26%) patients underwent an allogeneic haematopoietic stem cell transplant (HSCT) with an improved median OS compared to non-transplanted patients (non reached vs 8 months, P= 0.004). With a median follow up of 8.5 months, median OS was not reached. Survival analysis in subgroups will be available for the ASH meeting. Conclusion These data confirmed the efficacy and safety of CPX-351 in poor risk AML (t-AML and MRC-AML). The high rate of CR with low MRD compares favorably with previous report using 7+3 in elderly unfavorable AML (Sylvie D. Freeman et al., JCO 2013) and may explain the favorable outcome observed in patients after HSCT. Moreover, CPX-351 erases the poor prognosis associated with unfavorable mutations defined in 2017 ELN risk stratification. Lindsley's classifier was the best prognostic scoring system in patients treated by CPX-351. Disclosures Bertoli: Daiichi Sankyo: Consultancy; Astellas: Consultancy, Honoraria; Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria. Peterlin:Jazz Pharma: Consultancy; AbbVie Inc: Consultancy; Astellas: Consultancy; Daiichi-Sankyo: Consultancy. Chevallier:Incyte: Consultancy, Honoraria; Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria. Thomas:INCYTE: Honoraria; DAICHI: Honoraria; PFIZER: Honoraria; ABBVIE: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Pigneux:Daichi: Honoraria; Abbvie: Honoraria; Jazz: Honoraria; Astellas: Honoraria; Roche: Honoraria; Pfizer: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Recher:Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ades:Amgen: Research Funding; Helsinn Healthcare: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Cluzeau:Abbvie: Consultancy; Jazz Pharma: Consultancy; Menarini: Consultancy.
Published: 2019
Full Text: View/download PDF

27. FLT3 ligand plasma levels in acute myeloid leukemia

Author: Nelly Robillard, Alice Garnier, Soraya Wuilleme, Marion Eveillard, Olivier Theisen, Patrice Chevallier, Michel Chérel, Yannick Le Bris, Thierry Guillaume, Nicolas Blin, Steven Le Gouill, Camille Debord, Beatrice Mahe, Philippe Moreau, Pierre Peterlin, Amandine Le Bourgeois, Viviane Dubruille, Catherine Godon, Anne Lok, Joëlle Gaschet, Thomas Gastinne, Antoine Bonnet, Marie-Christine Béné, Cyrille Touzeau, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service d'Hématologie Biologique [CHU Nantes], Unité de Médecine Nucléaire [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), This study was supported by a grant from the DHU Oncogreffe of Nantes., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Acute Myeloid Leukemia, Myeloid, Time Factors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Online Only Articles, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Proportional Hazards Models, 0303 health sciences, business.industry, Myeloid leukemia, Disease Management, Membrane Proteins, Hematology, Plasma levels, Induction Chemotherapy, medicine.disease, Prognosis, cytokines, Leukemia, Leukemia, Myeloid, Acute, Adult Acute Lymphoblastic Leukemia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Flt3 ligand, business, Biomarkers
Abstract: International audience; no abstract
Published: 2019
Full Text: View/download PDF

28. Scoring System Based on Post-Transplant Complications in Patients after Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Study from the SFGM-TC

Author: Yves Beguin, Elodie Drumez, Mauricette Michallet, Bruno Lioure, Jordan Gauthier, Martin Carre, Stephane Vigouroux, Didier Blaise, Ibrahim Yakoub-Agha, Patrice Chevallier, Felipe Suarez, Anne Huynh, Charles Dauriac, Marie Robin, Jacques-Olivier Bay, Pierre-Simon Rohrlich, Jérôme Cornillon, Jean-Henri Bourhis, Alexis Caulier, Federico Garnier, Régis Peffault de Latour, Yohan Desbrosses, Alain Duhamel, Stéphanie Nguyen, CHADEYRON, DOMINIQUE, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Adult, Male, 0301 basic medicine, Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, Scoring system, Graft vs Host Disease, Predictor variables, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Transplantation, Homologous, In patient, ComputingMilieux_MISCELLANEOUS, Aged, Hematopoietic cell, Platelet recovery, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, Prognosis, Survival Analysis, Post transplant, 3. Good health, Transplantation, Treatment Outcome, 030104 developmental biology, Research Design, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Landmark analysis, Female, France, business
Abstract: Purpose We developed a prognostic scoring system to evaluate the prognosis of myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic hematopoietic cell transplantation after (allo-HCT). Patients and methods We performed a landmark analysis on a derivation cohort of 393 cases to identify prognostic factors for 3-year overall survival. Potential predictor variables included demographic and clinical data, transplantation modalities and early post-transplant complications. The scoring system was tested against a validation cohort which included 391 patients. Results Complications occurring before day 100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7; 95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points) were the only independent predictors of 3-year OS. The 3-year OS associated with low (0), intermediate (1-3) and high (≥4) risk scores was respectively 70%, 46% and 6%. The model performed consistently in both cohorts, with good calibration. Conclusion This post-transplant scoring system is a powerful predictor of outcome after allo-HCT for MDS, and can provide useful guidance for clinicians. Additional studies are required to evaluate this scoring system for other hematologic malignancies.
Published: 2019

29. The odyssee study: prevention of dysbiosis complications with autologous fecal microbiota transfer (fmt) in acute myeloid leukemia (aml) patients undergoing intensive treatment: results of a prospective multicenter trial

Author: Joël Doré, Mauricette Michallet, Simona Lapusan, Florent Malard, Patrice Chevallier, Sophie Ducastelle-Lepretre, Suzanne Tavitian, Colombe Saillard, Stephanie Nguyen-Quoc, Xavier Thomas, Emilie Plantamura, Pierre Peterlin, Clément Rocher, Lilia Boucinha, Anne Vekhoff, Françoise Huguet, Ollivier Legrand, Evelyne D'Incan, Anne-Sophie Michallet, Christian Recher, Etienne Paubelle, Cyrielle Gasc, Jerome Rey, Lila Gilis, Mohamad Mohty, Françoise Isnard, Marie Virginie Larcher, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Service d'hématologie, Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MaaT Pharma [Lyon], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MaaT Pharma, and American Society of Hematology (ASH). USA.
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Population, Biochemistry, law.invention, 03 medical and health sciences, Randomized controlled trial, law, Internal medicine, Multicenter trial, medicine, Clinical endpoint, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, Induction chemotherapy, Cell Biology, Hematology, medicine.disease, Chemotherapy regimen, 3. Good health, 030104 developmental biology, business, Dysbiosis
Abstract: Introduction. AML standard intensive induction chemotherapy ("3+7" or equivalent) combined with wide spectrum antibiotics can dramatically alter the composition of the gut microbiota, leading to dysbiosis which is characterized by loss of microbial diversity. Such dysbiosis status can promote a pathological condition involving uncontrolled local immune responses, systemic inflammation and increased incidence of adverse events. The development of FMT-based drugs to restore microbial communities could offer novel therapeutic possibilities to reduce such adverse events and potentially improve outcomes in AML. We therefore conducted this single arm prospective phase I/II multicenter trial (NCT02928523) to evaluate the use of a FMT-based drug in association with AML induction treatment to restore the gut microbiota diversity. Patients and methods. A total of 62 consecutive patients aged between 24 and 69 years old with a diagnosis of de novo AML were screened in 7 French sites. At time of admission and AML diagnosis (Step 1=S1), patients' faeces were collected, rigorously screened, prepared following a standardized process, and stored at -80°C until later administration. The drug was administered as an enema after hematopoietic recovery (S2) and before consolidation chemotherapy (Conso). The primary endpoint was the recovery of at least 70% of microbiota diversity (based on the Simpson index) after drug administration and the reduction of multidrug resistant bacteria carriage. Blood and feces samples were collected at S1, S2, and around 10 days post-FMT before Conso (S3). Microbiome diversity restoration was assessed by metagenomics analysis through Illumina HiSeq shotgun sequencing. Antibiotic resistance gene carriage (ARGC, also known as resistome) was evaluated through mapping of readouts on the MEGARES database. Secondary objectives included safety and analysis of host response with assessment of blood and fecal markers by ELISA and Luminex. Results. Overall, 25 patients were actually treated with FMT, and 20 were included in the per-protocol population. Induction Chemotherapy (IC) induced a dramatic shift in microbial communities, with a significant 42.3% decrease of mean α-diversity Simpson index between S1 and S2 at species level (0.85 to 0.50; p No serious adverse events (SAE) were observed within 30 days after FMT and all post FMT SAEs were not related to the FMT procedure. Moreover, FMT did not induce any local or systemic inflammatory reaction as measured by fecal and blood markers (fecal neopterin and IgA; plasmatic CRP, IL-6 and sCD14). Interestingly, restoration of the microbiome diversity was associated with a significant reduction of CRP and fecal neopterin levels, suggesting a potential anti-inflammatory impact of FMT. Overall, FMT was well tolerated and had an excellent safety profile. The one-year overall survival estimate in the whole cohort was 84% (4 deaths among 25, none of which were related to FMT: 2 multiple organ failures, 1 heart attack and 1 grade IV resistant GVHD). The median time to death from the second FMT was 182.5 days (113-225 days). Conclusions. This is the first prospective trial testing the safety and efficacy of FMT in AML patients receiving intensive induction chemotherapy. The trial achieved its primary endpoint and established the capacity of FMT to restore a diverse microbiome with high levels of similarity to baseline, as well as reducing ARGC and intestinal inflammation. A controlled randomized trial with repeated FMT administrations is currently planned to further evaluate the impact of FMT on clinical outcomes and long-term survival. (This trial was funded by MaaT Pharma whose product was tested in this protocol). Disclosures Mohty: MaaT Pharma: Consultancy, Honoraria. Doré:MaaT Pharma: Consultancy, Honoraria.
Published: 2018
Full Text: View/download PDF

30. Hematopoietic stem cell transplantation for patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a retrospective study of 21 patients from SFGM-TC centers

Author: Alban Villate, Marie-Thérèse Rubio, Patrice Chevallier, Ibrahim Yakoub-Agha, Reza Tabrizi, Pierre-Simon Rohrlich, Nicolas Vallet, Louis Terriou, Jonathan Farhi, Deborah Desmier, Fiorenza Barraco, Raynier Devillier, Natacha Maillard, Mohamad Mohty, Régis Peffault de Latour, Annalisa Ruggeri, Patrice Ceballos, Steéphanie Nguyen, Gaelle Guillerm, Flore Sicre de Fontbrune, Michael Loschi, Xavier Poiré, Gérard Socié, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service Hématologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Hôpital l'Archet, Hôpital Lapeyronie [Montpellier] (CHU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Hemoglobinuria, Paroxysmal, CD59, Hematopoietic stem cell transplantation, Antibodies, Monoclonal, Humanized, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Registries, Online Only Articles, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, Hematopoietic stem cell, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Eculizumab, medicine.disease, Hemolysis, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Monoclonal, Paroxysmal nocturnal hemoglobinuria, Hemoglobinuria, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder which manifests with hemolysis (classical PNH) due to loss of expression of the CD55 and CD59 proteins, which leads to complement mediated cell lysis.[1][1] Despite being the only curative treatment for PNH
Published: 2018
Full Text: View/download PDF

31. Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial

Author: Norbert Vey, Marie C. Béné, F. Huguet, Yves Chalandon, Véronique Lhéritier, Hervé Dombret, Philippe Rousselot, Xavier Thomas, Vahid Asnafi, Mathilde Hunault, S. Chevret, Elizabeth Macintyre, Agnès Buzyn, Patrice Chevallier, Martine Escoffre-Barbe, Caroline Bonmati, Thibaut Leguay, Thomas Pabst, Eric Delabesse, Jean-Yves Cahn, Nicolas Boissel, Jean-Pierre Marolleau, Stéphane Leprêtre, Norbert Ifrah, CHU Toulouse [Toulouse], Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’hématologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hématologie-oncologie adultes, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service d’Hématologie Adulte [Hôpitaux de Brabois, CHU Nancy], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Amiens-Picardie, Inselspital Bern, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Coordination du Groupe GRAALL [CH Lyon-Sud], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Swiss Group for Clinical Cancer Research [Bern, Switzerland], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Univ Angers, Okina, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Cancer Research, medicine.medical_specialty, Randomization, Cyclophosphamide, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Context (language use), 610 Medicine & health, Disease-Free Survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Antineoplastic Agents, Alkylating, Aged, ddc:616, Chemotherapy, business.industry, Hazard ratio, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, Tolerability, 030220 oncology & carcinogenesis, Adult Acute Lymphoblastic Leukemia, Female, business, 030215 immunology, medicine.drug
Abstract: Purpose To evaluate randomly the role of hyperfractionated cyclophosphamide (hyper-C) dose intensification in adults with newly diagnosed Philadelphia chromosome–negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol and to determine the upper age limit for treatment tolerability in this context. Patients and Methods A total of 787 evaluable patients (B/T lineage, 525 and 262, respectively; median age, 36.1 years) were randomly assigned to receive a standard dose of cyclophosphamide or hyper-C during first induction and late intensification. Compliance with chemotherapy was assessed by median doses actually received during each treatment phase by patients potentially exposed to the full planned doses. Results Overall complete remission (CR) rate was 91.9%. With a median follow-up of 5.2 years, the 5-year rate of event-free survival (EFS) and overall survival (OS) was 52.2% (95% CI, 48.5% to 55.7%) and 58.5% (95% CI, 54.8% to 61.9%), respectively. Randomization to the hyper-C arm did not increase the CR rate or prolong EFS or OS. As a result of worse treatment tolerance, advanced age continuously affected CR rate, EFS, and OS, with 55 years as the best age cutoff. At 5 years, EFS was 55.7% (95% CI, 51.8% to 59.4%) for patients younger than 55 years of age versus 25.8% (95% CI, 19.9% to 35.6%) in older patients (hazard ratio, 2.16; P < .001). Patients ≥ 55 years of age, in whom a lower compliance to the whole planned chemotherapy was observed, benefited significantly from hyper-C, whereas younger patients did not. Conclusion No significant benefit was associated with the introduction of a hyper-C sequence into a frontline pediatric-like adult acute lymphoblastic leukemia therapy. Overall, tolerability of an intensive pediatric-derived treatment was poor in patients ≥ 55 years of age.
Published: 2018
Full Text: View/download PDF

32. Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the acute leukemia working party of European group of Bone Marrow Transplantation

Author: Raynier Devillier, Gabrielle Roth-Guepin, Anne Huynh, Myriam Labopin, Ghulam J. Mufti, Gérard Socié, Nathalie Fegueux, Jean-Yves Cahn, Fabio Ciceri, Arnon Nagler, Deborah Desmier, Frédéric Baron, Mohamad Mohty, Jean Bourhis, Didier Blaise, Marie Pierre Ledoux, Patrice Chevallier, Mauricette Michallet, Département d'Hématologie [Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Unité de Transplantation et de Thérapie Cellulaire [Marseille], Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), King's College Hospital (KCH), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Hôpital Lapeyronie [Montpellier] (CHU), IRCCS Ospedale San Raffaele [Milan, Italy], Université de Liège, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Devillier, Raynier, Labopin, Myriam, Chevallier, Patrice, Ledoux, Marie-Pierre, Socié, Gérard, Huynh, Anne, Bourhis, Jean-Henri, Cahn, Jean-Yve, Roth-Guepin, Gabrielle, Mufti, Ghulam, Desmier, Déborah, Michallet, Mauricette, Fegueux, Nathalie, Ciceri, Fabio, Baron, Fréderic, Blaise, Didier, Nagler, Arnon, and Mohty, Mohamad
Subjects: Adult, Male, medicine.medical_specialty, Allogeneic transplantation, Transplantation Conditioning, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Survival analysis, Aged, Antilymphocyte Serum, Retrospective Studies, Acute leukemia, Transplantation, Dose-Response Relationship, Drug, business.industry, Siblings, Hazard ratio, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, medicine.disease, Survival Analysis, Tissue Donors, 3. Good health, Leukemia, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Female, business, 030215 immunology
Abstract: International audience; Antithymocyte globulin (ATG) is commonly used for graft-vs.-host disease (GVHD) prophylaxis in unrelated donor allogeneic transplantation (Allo-HSCT). However, its use is still controversial in matched sibling donor (MSD) Allo-HSCT, notably after reduced intensity conditioning (RIC). ATG dose may influence the outcome, explaining in part the discordant conclusions in MSD Allo-HSCT. We, therefore, analyzed the impact of ATG doses in patients with acute myeloid leukemia in first complete remission undergoing RIC Allo-HSCT from a MSD. We analyzed 234 patients from the EBMT registry and compared outcome according to given ATG dose (high dose: >= 6 mg/kg, n = 39 or low dose: < 6 mg/kg, n = 195). No difference was found in the cumulative incidence of acute (grade 2-4: high dose vs. low dose: 21% vs. 13%, p = 0.334; adjusted hazard ratio (HR): 1.20, p =0.712) and chronic GVHD (extensive: high dose vs. low dose: 19% vs. 18%, p = 0.897; adjusted HR: 1.01, p = 0.980). In contrast, high dose of ATG significantly increased the incidence of relapse (52% vs. 26%, p = 0.011; adjusted HR: 1.31, p = 0.001) leading to impaired outcome (HR progression-free survival (PFS): 1.23, p = 0.002; HR overall survival (OS): 1.17, p = 0.029; HR GVHD and relapse-free survival (GRFS): 1.20, p = 0.005). We conclude that an ATG dose
Published: 2018
Full Text: View/download PDF

33. Clofarabine/busulfan-based reduced intensity conditioning regimens provides very good survivals in acute myeloid leukemia patients in complete remission at transplant: a retrospective study on behalf of the SFGM-TC

Author: Hélène Labussière Wallet, Mohamad Mohty, Régis Peffault de Latour, Mathieu Leclerc, Didier Blaise, Marie-Thérèse Rubio, Patrice Chevallier, Jean-Henri Bourhis, Corentin Orvain, Karin Bilger, Patrice Ceballos, Myriam Labopin, Thierry Guillaume, Amandine Le Bourgeois, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Henri Mondor, Univ Angers, Okina, Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'Hématologie Biologique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Hospices Civils de Lyon (HCL), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], acute myeloid leukemia, 03 medical and health sciences, 0302 clinical medicine, Median follow-up, allogeneic stem cell transplantation, Internal medicine, hemic and lymphatic diseases, Medicine, Clofarabine, busulfan, Gynecology, Hematology, business.industry, Myeloid leukemia, 3. Good health, Fludarabine, Transplantation, [SDV] Life Sciences [q-bio], Regimen, Oncology, clofarabine, reduced intensity conditioning regimen, 030220 oncology & carcinogenesis, business, Busulfan, 030215 immunology, medicine.drug, Research Paper
Abstract: // Amandine Le Bourgeois 1 , Myriam Labopin 2 , Mathieu Leclerc 3 , Regis Peffault de Latour 4 , Jean-Henri Bourhis 5 , Patrice Ceballos 6 , Corentin Orvain 7 , Helene Labussiere Wallet 8 , Karin Bilger 9 , Didier Blaise 10 , Marie-Therese Rubio 11 , Thierry Guillaume 1 , Mohamad Mohty 2 , Patrice Chevallier 1 and on behalf of Societe Francophone de Greffe de Moelle et de Therapie Cellulaire 1 Department of Hematology, CHU Hotel Dieu, Nantes, France 2 Department of Hematology, Hopital Saint Antoine, Paris, France 3 Department of Hematology, Hopital Henri Mondor, Creteil, France 4 Department of Hematology, Hopital Saint Louis, Universite Paris 7, Denis Diderot, Paris, France 5 Department of Hematology, Hopital Gustave Roussy, Paris, France 6 Department of Hematology, CHU de Montpellier, Montpellier, France 7 Department of Hematology, CHU d’Angers, Angers, France 8 Department of Hematology, Centre Hospitalier Lyon Sud, Lyon, France 9 Department of Hematology, CHU Strasbourg, Strasbourg, France 10 Department of Hematology, Centre de Recherche en Cancerologie de Marseille, Institut Paoli Calmettes, Marseille, France 11 Department of Hematology, CHU Nancy, Nancy, France Correspondence to: Amandine Le Bourgeois, email: amandine.lebourgeois@chu-nantes.fr Patrice Chevallier, email: patrice.chevallier@chu-nantes.fr Keywords: allogeneic stem cell transplantation; clofarabine; busulfan; reduced intensity conditioning regimen; acute myeloid leukemia Received: August 24, 2018 Accepted: November 01, 2018 Published: November 27, 2018 ABSTRACT Background: Clofarabine has been proved to have higher anti-leukemic myeloid activity compared to fludarabine, a drug extensively used as part of reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT). Results: Eighty-four patients were included. The majority of patients had acute myeloid leukemia (AML, n = 63). Sixty-one patients were in complete remission (AML n = 55). With a median follow up of 31 months (range: 5.7–74.1), 2-year overall (OS) and disease-free (DFS) survivals, relapse incidence (RI), non-relapse mortality (NRM) and graft-versus-host disease (GVHD)/relapse free survival (GRFS) were 64.5% (53.8–75.2); 57.2% (46.2–68.2); 27.7% (18.2–37.9); 15.1% (8.2–23.9) and 43.6% (32.5–54.7), respectively. Considering AML in remission, 2-year OS, DFS, RI, NRM and GRFS were 74.2% (62–86.5); 66.8% (53.6–79.9); 23.4% (12.7–36); 9.8% (3.5–19.9) and 50.9% (36.9–64.9), respectively. Two-year outcomes were similar between CloB2A1 and CloB2A2 sub-groups. In multivariate analysis, active disease at transplant was the only factor adversely impacting 2 years outcomes. Conclusions: CloB2A2/A1 RIC regimen provides very good results for AML patients allografted in CR and could be retained as a new RIC platform for these patients. Materials and Methods: This was a retrospective study including all patients who received a clofarabine/busulfan based RIC allo-SCT for myeloid malignancies and reported within the SFGM-TC registry. RIC regimen consisted of clofarabine 30 mg/m²/day 4 to 5 days (Clo), busulfan 3.2 mg/kg/day 2 days (B2) and 2.5 mg/kg/day of rabbit anti-thymocyte globulin 1 or 2 days (A1 or A2). The primary objective of the study was to report the main outcomes of the whole cohort at 2 years.
Published: 2018
Full Text: View/download PDF

34. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study

Author: Katie S. Gatwood, Jordi Esteve, Patrice Chevallier, Peter Dreger, Matthias Stelljes, Myriam Labopin, Bipin N. Savani, Norbert Claude Gorin, Arnold Ganser, Audrey Mailhol, Juergen Finke, Dietrich W. Beelen, Sebastian Giebel, Ghulam J. Mufti, Gerhard Ehninger, Arnon Nagler, Christoph Schmid, Frédéric Baron, Didier Blaise, Ariane Boumendil, Dietger Niederwieser, Mohamad Mohty, Fabio Ciceri, Salyka Sengsayadeth, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Hannover Medical School [Hannover] (MHH), Westfälische Wilhelms-Universität Münster (WWU), University of Münster, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Dept. of Bone Marrow Transplantation, University Hospital, Essen, University Hospital Essen, Division Hematology, Oncology and Hemostasiology [Leipzig, Germany], University Hospital in Leipzig [Germany], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Department of Medicine V, Universität Heidelberg [Heidelberg], King's College Hospital (KCH), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (DRPH/SRBE/LTCRA), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), IRCCS Ospedale San Raffaele [Milan, Italy], Université de Liège, Ludwig Maximilian University [Munich] (LMU), Cancer Center Gliwice, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Sengsayadeth, Salyka, Labopin, Myriam, Boumendil, Ariane, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gatwood, Katie S., Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N., Nagler, Arnon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (IRSN/DRPH/SRBE/LTCRA), Service de RadioBiologie et d'Epidémiologie (IRSN/DRPH/SRBE), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
Subjects: Adult, Male, medicine.medical_specialty, Secondary, Transplantation Conditioning, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Hematopoietic stem cell transplantation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Secondary Acute Myeloid Leukemia, Cumulative incidence, ddc:610, Aged, Bone Marrow Transplantation, Aged, 80 and over, Acute leukemia, Univariate analysis, Transplantation, Acute myeloid leukemia, Toxicity, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Confidence interval, 3. Good health, Allogeneic stem cell transplantation, Europe, Antileukemic effect, Leukemia, Myeloid, Acute, Treatment Outcome, 030220 oncology & carcinogenesis, Female, business, 030215 immunology, Conditioning
Abstract: International audience; Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [Cl], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% Cl, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (
Published: 2018
Full Text: View/download PDF

35. Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome Patients with a 5q Deletion

Author: Pavel Jindra, Rik Schots, Dietrich W. Beelen, Laurent Garderet, Simona Iacobelli, Stig Lenhoff, Didier Blaise, Xavier Poiré, Arnon Nagler, Dimitris Ziagkos, Charles Craddock, Per Ljungman, Patrice Chevallier, Ibrahim Yakoub-Agha, Nicolaus Kröger, Jakob Passweg, Nicolaas Schaap, Jaime Sanz, Marie Robin, Alessandro Rambaldi, Liisa Volin, Anja van Biezen, Ghulam J. Mufti, Jürgen Finke, Johan Maertens, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinicum, Hematologian yksikkö, Department of Oncology, HUS Comprehensive Cancer Center, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Immunology and Microbiology, Laboratory of Molecullar and Cellular Therapy, Clinical sciences, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service d'hématologie
Subjects: Male, BLOOD, Databases, Factual, IMPACT, CHROMOSOME, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Hematopoietic stem cell transplantation, PROGNOSTIC SCORING SYSTEM, Gastroenterology, 0302 clinical medicine, Recurrence, hemic and lymphatic diseases, MDS, Cumulative incidence, LENALIDOMIDE, Incidence, Incidence (epidemiology), Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, TP53 MUTATIONS, EUROPEAN-SOCIETY, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, WORKING PARTY, Chromosomes, Human, Pair 5, Female, Chromosome Deletion, Life Sciences & Biomedicine, DEL(5Q), del (5q), medicine.drug, Adult, medicine.medical_specialty, Immunology, 3122 Cancers, Disease-Free Survival, Settore MED/01 - Statistica Medica, 03 medical and health sciences, Sex Factors, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Humans, MARROW-TRANSPLANTATION, Survival rate, Lenalidomide, Transplantation, Science & Technology, business.industry, Myelodysplastic syndromes, medicine.disease, Allogeneic stem cell transplantation, Myelodysplastic Syndromes, business, 030215 immunology
Abstract: The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities (del [5q]+) are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+ . A total of 162 patients, of median age 54 years (range, 9 to 73), having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46% (95% CI, 38 to 54), whereas the estimated 4 year survival, relapse-free and overall, was 25% (95% CI, 18 to 33) and 30% (95% CI, 23 to 38), respectively. In a multivariate analysis patients with del (5q) and a blast excess displayed poorer survival (hazard ratio, 2.38; 95% CI, 1.44 to 3.93; P
Published: 2018
Full Text: View/download PDF

36. Allogeneic Hematopoietic Stem Cell Transplantation Improves Outcome of Elderly Patients with Acute Myeloid Leukemia in First Complete Remission: A Time-Dependent and Multistate Analysis from the French Innovative Leukemia Organization

Author: Mathilde Hunault, Yosr Hicheri, Christian Recher, Raynier Devillier, Bruno Lioure, Norbert Ifrah, Claude-Eric Bulabois, Pierre Peterlin, Didier Blaise, Gabrielle Roth Guepin, Alice Garnier, Gaelle Guillerm, Pierre-Yves Dumas, Norbert Vey, Jean-Yves Cahn, Marie-Thérèse Rubio, Patrice Chevallier, Edouard Forcade, Sylvain Thepot, Arnaud Pigneux, Anne Huynh, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Hematopoietic stem cell transplantation, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 10. No inequality, Proportional hazards model, business.industry, Complete remission, Myeloid leukemia, Cell Biology, Hematology, medicine.disease, Chemotherapy regimen, 3. Good health, Transplantation, Leukemia, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, business
Abstract: Allogeneic stem cell transplantation (AlloSCT) is a curative option for acute myeloid leukemia (AML) patients. In first complete remission (CR1), young patients (< 60 years) with intermediate or unfavorable ELN disease risk are usually considered for AlloSCT. In contrast, because of the expected higher toxicity in older patients, the benefit of this treatment remains a matter of debate after 60 years, especially in the intermediate ELN risk group. In this multicenter analysis from the French Innovative Leukemia Organization (FILO), we investigated whether AlloSCT was beneficial for AML patients over 60 years old in CR1. Inclusion criteria were: patients between 60 and 70 years of age diagnosed with AML from 2007 to 2017; CR1 after intensive chemotherapy; ELN-2010 intermediate or unfavorable risk group. AlloSCT was evaluated as a time dependent variable in survival calculations and in a multivariate Cox model adjusted on age, ELN group, transplantation period and stratified by transplantation center. We also used a multistate model as follow: initial state for all patients was "No Allo - CR" with time 0 at the time of CR. From initial state, patients can transit to "Allo-CR", or move through 2 absorbing states (non-relapse death (No Allo-NRM) or relapse (No Allo-Relapse). Similarly, once transplanted (i.e. in the state "Allo-CR"), patients can move to "Allo-Relapse" or "Allo - NRM" when such events occurred. The model allows the dynamic prediction of probability for a patient to be in a specific state considering specific initial state and time. We analyzed 521 consecutive patients in 6 centers who matched inclusion criteria. Median age was 65 years (range: 60-70). ELN-2010 risk was intermediate and unfavorable in 376 (72%) and 145 (28%) patients, respectively. While all patients had a theoretical indication for AlloSCT in CR1, 199 (38%) were actually transplanted (129 (34%) and 70 (48%) in the intermediate and unfavorable risk group, respectively). In the whole cohort, AlloSCT as time-dependent variable significantly improved relapse-free survival ([RFS] at 5 years, No AlloSCT vs. AlloSCT: 14% vs. 47% p < 0.001) and overall survival ([OS] at 5 years, No AlloSCT vs. AlloSCT: 24% vs. 51% p < 0.001). In subgroup analysis based on ELN-2010 risk classification, AlloSCT significantly improved outcome of both ELN intermediate (No AlloSCT vs. AlloSCT: 5-y RFS: 16% vs. 50% p < 0.001; 5-y OS: 26% vs. 54% p < 0.001) and unfavorable (No AlloSCT vs. AlloSCT: 5-y RFS: 7% vs. 44% p < 0.001; 5-y OS: 17% vs. 46% p < 0.001) risk group patients (Figure A and B). By multivariate time-dependent Cox model, AlloSCT significantly decreased the risk of relapse (HR [95%CI]: 0.29 [0.20-0.41] p < 0.001) and increased the risk of NRM (HR [95%CI]: 2.61 [1.38-4.94] p = 0.003). This led to a significant advantage for AlloSCT in both RFS (HR [95%CI]: 0.48 [0.36-0.64] p < 0.001) and OS (HR [95%CI]: 0.60 [0.44-0.81] p = 0.001). This benefit was observed in both intermediate and unfavorable ELN-2010 risk groups, with lower risk of relapse (intermediate: HR [95%CI]: 0.30 [0.19-0.46] p < 0.001; unfavorable: HR [95%CI]: 0.37 [0.19-0.72] p = 0.004) and better OS (intermediate: HR [95%CI]: 0.67 [0.47-0.96] p = 0.028; unfavorable: HR [95%CI]: 0.51 [0.29-0.91] p = 0.022). Multistate model showed that 5 years after CR1, few patients were still alive in CR without AlloSCT (i.e. in the initial "No Allo-CR" state), whatever the ELN-2010 risk group (intermediate: 9%; unfavorable: 1% Figure C and D). Among patients who were transplanted, the probability for transiting to Allo-NRM state within 5 years post CR1 was 17% and 24% in intermediate and unfavorable ELN-2010 groups, respectively. Corresponding values for patients without AlloSCT transiting to No Allo-NRM state were 11% and 12%. Moreover, considering a landmark at 6 months after CR1, the multistate model showed that patients who received AlloSCT had lower probability of relapse at 5 years (22% and 33% in intermediate and unfavorable ELN-2010 groups, respectively) compared to those who did not (68% and 78% in intermediate and unfavorable groups, respectively). AlloSCT for CR1 AML patients over 60 years of age is routinely feasible and significantly improves outcome in both intermediate and unfavorable ELN-2010 risk groups. Less than 10% of patients are long term disease free survival without AlloSCT, even in intermediate risk group, supporting that AlloSCT remains the first curative option for these patients. Figure. Figure. Disclosures No relevant conflicts of interest to declare.
Published: 2018
Full Text: View/download PDF

37. Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study

Author: Sebastian Giebel, Arnold Ganser, Myriam Labopin, Audrey Mailhol, Peter Dreger, Gerhard Ehninger, Dietger Niederwieser, Ariane Boumendil, Dietrich W. Beelen, Norbert Claude Gorin, Salyka Sengsayadeth, Katie S. Gatwood, Fabio Ciceri, Jürgen Finke, Mohamad Mohty, Arnon Nagler, Matthias Stelljes, Patrice Chevallier, Ghulam J. Mufti, Frédéric Baron, Bipin N. Savani, Christoph Schmid, Didier Blaise, Maria H. Gilleece, Jordi Esteve, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sengsayadeth, Salyka, Gatwood, Katie S, Boumendil, Ariane, Labopin, Myriam, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gilleece, Maria H, Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N, and Nagler, Arnon
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Cumulative incidence, Registries, Survival rate, Aged, Retrospective Studies, Acute leukemia, Univariate analysis, Transplantation, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, food and beverages, Retrospective cohort study, Neoplasms, Second Primary, Hematology, Middle Aged, Allografts, 3. Good health, Survival Rate, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Myelodysplastic Syndromes, Female, business, 030215 immunology
Abstract: Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study. Median age of the cohort was 59.6 years (range, 18.6-78.6 years). Myeloablative conditioning (MAC) was given to 40% of patients, and 60% received reduced-intensity conditioning (RIC). Overall, the 2-year cumulative incidence of relapse (RI) was 37%, leukemia-free survival (LFS) was 40%, overall survival (OS) was 46%, nonrelapse mortality (NRM) was 23%, and chronic graft-versus-host disease (cGVHD) was 39%. In univariate analysis, a statistical difference between conditioning regimens 6 months after HCT in favor of the MAC group was noted with regard to RI (hazard ratio [HR], 1.47; P = .03), LFS (HR, 1.43; P = .01), and OS (HR, 1.55; P < .05). There was no difference in the cumulative incidence of NRM (HR, 1.38; P = .15). This effect was similarly seen in multivariate analysis (MVA): cumulative incidence of relapse (HR, 1.79; P < .05), LFS (HR, 1.43; P = .02), and OS (HR, 1.53; P = .005) with no difference in NRM (HR, 1; P = .98). This EBMT ALWP analysis suggests that long-term survival can be achieved in patients with sAML with antecedent MDS/MPN and that MAC is a suitable conditioning regimen in patients with sAML.
Published: 2018
Full Text: View/download PDF

38. Stratégies préventives et thérapeutiques de la rechute après allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Thierry Guillaume, Mauricette Michallet, Claude Eric Bulabois, Xavier Poiré, Stavroula Masouridi Levrat, Anne Huynh, Cécile Dumesnil, Ali Bazarbachi, Etienne Daguindau, Ibrahim Yakoub-Agha, Patrice Chevallier, Cécile Pautas, Anne-Lise Ménard, Nabil Yafour, Florence Beckerich, Aurélie Ravinet, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Rouen, Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), American University of Beirut [Beyrouth] (AUB), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), UCL - (SLuc) Service d'hématologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)
Subjects: 03 medical and health sciences, Cancer Research, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine, ComputingMilieux_MISCELLANEOUS, 3. Good health, 030215 immunology
Abstract: Resume La rechute reste la premiere cause de mortalite des hemopathies malignes apres allogreffe de cellules souches hematopoietiques (allo-CSH) (van den Brink et al., 2010). Le risque de recurrence de la maladie est eleve chez les patients presentant des marqueurs cytogenetiques ou moleculaires de mauvais pronostic, et/ou allogreffes en situation de maladie refractaire ou en remission hematologique sans reponse moleculaire ou radiologique (TEP-scan) complete. Dans le cadre des 7e ateliers d’harmonisation des pratiques de greffe de la Societe francophone de greffe de moelle et de therapie cellulaire (SFGM-TC), le groupe de travail s’est base sur les donnees de la litterature, afin d’elaborer des recommandations concernant la prevention et le traitement de la rechute post allo-CSH. Pour les LAM et les SMD a haut risque, une strategie de maintenance post-greffe est possible par des agents hypomethylants ou des ITK anti-FLT3 si la cible est presente. En ce qui concerne les LAL Phi+, un traitement de maintenance par ITK est un consensus. Pour les lymphomes, il n’existe pas a l’heure actuelle des donnees formelles concernant l’utilisation d’un traitement de maintenance systematique et une strategie preemptive basee sur l’immunomodulation, le suivi du chimerisme et l’injection des lymphocytes du donneur est recommandee. Pour le myelome multiple, meme si l’indication de l’allogreffe reste discutee, notre recommandation serait l’utilisation d’un traitement de maintenance par bortezomib, vue la bonne tolerance de ce traitement, sans augmentation du risque de GVHD.
Published: 2017
Full Text: View/download PDF

39. Impact of stem cell graft on early viral infections and immune reconstitution after allogeneic transplantation in adults

Author: Philippe Moreau, Lucie Planche, Céline Bressollette-Bodin, Berthe-Marie Imbert-Marcille, Mohamad Mohty, Marie Rimbert, Marina Illiaquer, Claire Le Houerou, Amandine Le Bourgeois, Pierre Peterlin, Alice Garnier, Thierry Guillaume, Patrice Chevallier, Laboratoire de Virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie Clinique [CHU Nantes], Département Promotion de la Recherche Clinique [CHU Nantes], Laboratoire d'Immunologie [CHU Nantes], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by two grants funded by the Laurette Fugain Association., and Bernardo, Elizabeth
Subjects: Adult, Male, Epstein-Barr Virus Infections, Allogeneic transplantation, viruses, Congenital cytomegalovirus infection, Roseolovirus Infections, Reduced intensity, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cord blood transplant, Biology, Opportunistic Infections, Umbilical cord, Virus, HHV-6, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Immune Reconstitution, [SDV.CAN] Life Sciences [q-bio]/Cancer, EBV, Virology, medicine, Humans, Transplantation, Homologous, Prospective Studies, Whole blood, Aged, Polyomavirus Infections, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, CMV, virus diseases, Middle Aged, medicine.disease, biology.organism_classification, 3. Good health, Regimen, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, Cytomegalovirus Infections, Human herpesvirus 6, Female, PBSC, 030215 immunology
Abstract: International audience; Background: Viral infections are well-known complications after allogeneic stem cell transplant (allo-SCT).Objectives: We compared prospectively incidences of DNAemia and active infections (AI) for five opportunistic viruses (Human Herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), Cytomegalovirus (CMV) and Adenovirus (ADV)) and kinetics of immune reconstitution (IR) in adults receiving either double umbilical cord blood (dUCB group) or unrelated peripheral blood stem cell (uPBSC group) allo-SCT after a reduced-intensity conditioning (RIC) regimen.Study design: Whole blood samples were collected at transplant, every 15 days during the first 3 months and at 4, 5 and 6 months post-transplant.Results: Sixty-five patients were enrolled (uPBSC n = 34; dUCB n = 31). Incidences of HHV-6 and BKPyV DNAemia were significantly higher for dUCB (97% vs 23.5% and 58% vs 32%, respectively) while EBV DNAemia was more frequently detected in uPBSC (71% vs 26%). The incidence of CMV DNAemia was similar between both groups. ADV AI developed only in dUCB. HHV-6 AI were also higher in dUCB (84% vs 21%). In multivariate analysis, dUCB graft was the only independent factor associated with HHV-6 DNAemia (OR: 19.0; 95%CI: 5.2–69.1; p < 0.0001) while EBV DNAemia were significantly associated with uPBSC (OR: 29.9; 95%CI: 5.68–158; p < 0.0001). dUCB graft was also the only factor associated with HHV-6 AI. Finally, higher counts and faster recoveries of B lymphocytes (p < 0.0001) and monocytes (p = 0.0007) were observed in the dUCB group.Conclusion: We demonstrate a strong correlation between sources of graft and patterns of viral DNAemia and AI and IR after RIC allo-SCT.
Published: 2017
Full Text: View/download PDF

40. Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord

Author: S. Vigouroux, L Souchet, Patrice Chevallier, Anne Sirvent, C-E. Bulabois, Faezeh Legrand, Laurence Clement, Jérôme Cornillon, S. Furst, Sébastien Maury, Vivien Béziat, J Lejeune, Bernard Rio, Sylvie Chevret, G Margueritte, Sylvie François, Karin Bilger, Vincent Vieillard, G. Michel, Madalina Uzunov, Gérard Socié, Marie-Cécile Michallet, Patrice Ceballos, V. Rocha, J.-O. Bay, N. Maillard, Charles Dauriac, I. Yakoub-Agha, Abla Achour, Anne Huynh, Stéphanie Nguyen, Institut des Matériaux Jean Rouxel (IMN), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Semiconductor Photonics Research Group, Trinity College Dublin-Science Foundation Ireland-Enterprise Ireland-Higher Education Authority, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), STMicroelectronics, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Public Henri Tudor [Technoport] (CRP Henri Tudor), Centre de Recherche Public Henri-Tudor [Luxembourg] (CRP Henri-Tudor), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de sismologie (DS (UMR_7580)), Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Centre National de la Recherche Scientifique (CNRS), Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel Dieu, IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel Dieu, Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Adult, Male, 0301 basic medicine, Transplantation Conditioning, Myeloid, Cord Blood Stem Cell Transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Multicenter trial, Humans, Medicine, Prospective Studies, Registries, ComputingMilieux_MISCELLANEOUS, Transplantation, business.industry, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Recovery of Function, Hematology, Middle Aged, Allografts, medicine.disease, 3. Good health, Killer Cells, Natural, Survival Rate, Leukemia, Myeloid, Acute, Leukemia, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, Immunology, Female, business, 030215 immunology
Abstract: Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.
Published: 2017
Full Text: View/download PDF

41. Reduced-intensity vs reduced-toxicity myeloablative fludarabine/busulfan-based conditioning regimens for allografted nonHodgkin lymphoma adult patients: a retrospective study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire

Author: E. Deconinck, S. Vigouroux, A. Le Bourgeois, J.-O. Bay, Aude Charbonnier, R. Peffault de Latour, Nathalie Contentin, Ibrahim Yakoub-Agha, Patrice Chevallier, M. Labopin, Patrice Ceballos, Jérôme Cornillon, Tony Marchand, S. Chantepie, Mélanie Mercier, Stéphanie Nguyen, Claude-Eric Bulabois, M. Mohty, Ambroise Marçais, Didier Blaise, N. Maillard, Pascal Turlure, Etienne Daguindau, P.S. Rorhlich, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Développement, institutions et analyses de long terme (DIAL), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Pierre et Marie Curie - Paris 6 (UPMC), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ALWP-EBMT & Département d'hématologie et de thérapie cellulaire [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz
Subjects: Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Graft vs Host Disease, Gastroenterology, conditioning regimen, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, allogeneic stem-cell transplantation, Humans, Cumulative incidence, busulfan, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Univariate analysis, business.industry, Incidence (epidemiology), Lymphoma, Non-Hodgkin, non-Hodgkin lymphoma, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Fludarabine, Lymphoma, Transplantation, Graft-versus-host disease, Oncology, 030220 oncology & carcinogenesis, Female, business, Busulfan, Vidarabine, 030215 immunology, medicine.drug
Abstract: Background Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet. Patients and methods This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 277) or at a myeloablative reduced-toxicity dose (FB3/FB4, 3 or 4 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 101). Results In univariate analysis, the 2-year overall survival (FB2 66.5% versus 60.3%, P = 0.33), lymphoma-free survival (FB2 57.9% versus 49.8%, P = 0.26), and non-relapse mortality (FB2 19% versus 21.1%, P = 0.91) were similar between both groups. Cumulative incidence of grade III–IV acute graft versus host disease (GVHD) (FB2 11.2% versus 18%, P = 0.08), extensive chronic GVHD (FB2: 17.3% versus 10.7%, P = 0.18) and 2-year GVHD free-relapse free survival (FB2: 44.4% versus 42.8%, P = 0.38) were also comparable. In multivariate analysis there was a trend for a worse outcome using FB3/FB4 regimens (overall survival: HR 1.47, 95% CI: 0.96–2.24, P = 0.08; lymphoma-free survival: HR: 1.43, 95% CI: 0.99–2.06, P = 0.05; relapse incidence: HR 1.54; 95% CI: 0.96–2.48, P = 0.07). These results were confirmed using a propensity score-matching strategy. Conclusion We conclude that reduced toxicity myeloablative conditioning with fludarabine/busulfan does not improve the outcomes compared with reduced-intensity conditioning in adults receiving allo-SCT for NHL.
Published: 2017
Full Text: View/download PDF

42. Impact of body-surface area on patients' outcome in younger adults with acute myeloid leukemia

Author: Yosr Hicheri, Norbert Vey, Jean-Yves Cahn, Patrice Chevallier, Fabrice Larosa, Norbert Ifrah, Martin Carre, Emmanuel Gyan, Bouscary Didier, Chantal Himberlin, Bruno Lioure, Gaelle Guillerm, Christian Recher, Mario Ojeda-Uribe, Marie C. Béné, Marc Bernard, Caroline Bonmati, Arnaud Pigneux, Mathilde Hunault-Berger, Xavier Cahu, Jacques Delaunay, Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [Nantes], Centre d'investigation clinique en cancérologie (CI2C), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], PRES Université Nantes Angers Le Mans (UNAM), Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Rennes (UR)-Hôpital Pontchaillou, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Body Surface Area, medicine.medical_treatment, [SDV]Life Sciences [q-bio], acute myeloid leukemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Multicenter Studies as Topic, Medicine, Body Weights and Measures, Young adult, Dose intensity, Survival analysis, Body surface area, Chemotherapy, business.industry, Remission Induction, Age Factors, Myeloid leukemia, Hematology, General Medicine, Survival Analysis, 3. Good health, Surgery, Leukemia, Myeloid, Acute, Treatment Outcome, Clinical Trials, Phase III as Topic, Postremission Therapy, dose reduction, Younger adults, 030220 oncology & carcinogenesis, Cytarabine, Female, body-surface area, business, 030215 immunology, medicine.drug
Abstract: International audience; OBJECTIVES: Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, and clinical outcome. METHODS: The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered. RESULTS: Very high BSA (≥2.15 m(2) ) was the factor most significantly associated with the physician's decision to reduce chemotherapy doses during induction and postremission therapy. Despite similar AML characteristics and therapeutic strategies, the very high BSA group exhibited a significantly worse survival (5-years OS of 27%) compared to the low (BSA≤1.5 m(2) ), intermediate (1.5 m(2)
Published: 2017
Full Text: View/download PDF

43. Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study

Author: M C Béné, Françoise Huguet, Chantal Himberlin, Norbert Ifrah, Marina Lafage-Pochitaloff, Marc Renaud, Patrice Chevallier, Pascal Turlure, K. Beldjord, Françoise Isnard, B. Lioure, Xavier Thomas, Véronique Lhéritier, Mathilde Hunault, E. Tavernier, Vahid Asnafi, Hervé Dombret, A. Charbonnier, A. Desjonquères, Jacques-Olivier Bay, Stéphane Leprêtre, Thibaut Leguay, J. N. Bastie, Marc Bernard, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'hématologie [Institut de Cancérologie de la Loire], Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie Clinique [CHU Reims], Hôpital universitaire Robert Debré [Reims], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Male, Survival, analysis, medicine.medical_treatment, Hematopoietic stem cell transplantation, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Philadelphia Chromosome, Young adult, Child, Hematology, Leukemia, Remission Induction, Hematopoietic Stem Cell Transplantation, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Treatment Outcome, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Imatinib Mesylate, Female, Original Article, France, Rituximab, Adult, medicine.medical_specialty, Adolescent, Patients, [SDV.CAN]Life Sciences [q-bio]/Cancer, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Disease-Free Survival, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Transplantation, Homologous, Molecular Biology, therapy, business.industry, medicine.disease, Transplantation, Clinical trial, Immunology, Multivariate Analysis, Adult Acute Lymphoblastic Leukemia, business, Laboratories, 030215 immunology
Abstract: The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph− ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph− ALL younger adults (18–63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14–24%) and 13.3% (8–18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21–38%) and 25% (17–33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (PP=0.004, respectively) and longer OS (P=0.004 and P
Published: 2016
Full Text: View/download PDF

44. Impact of Thymoglobulin by Stem Cell Source (Peripheral Blood Stem Cell or Bone Marrow) After Myeloablative Stem Cell Transplantation From HLA 10/10-Matched Unrelated Donors. A Report From the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Author: Gérard Socié, Mohamad Mohty, Clémence Deteix, Tony Marchand, Natacha Maillard, Felipe Suarez, Aurélie Cabrespine, Jacques-Olivier Bay, Anne Huynh, Sébastien Maury, Aurélie Ravinet, Stéphanie Nguyen, Anne Lise Menard, Régis Peffault de Latour, Mauricette Michallet, Jill Patrice Cassuto, Ibrahim Yakoub Agha, Noel Milpied, Patrice Chevallier, Oumedaly Reman, Service d’Hématologie Clinique Adulte et de Thérapie Cellulaire, CHU Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Haematology, CHU Bordeaux [Bordeaux], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service Hématologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), INSERM U955, équipe 7, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), APHP Henri Mondor, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Henri Mondor, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Henri Mondor [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire de Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I ( UdA ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Hôpital Jean Bernard, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB)
Subjects: Male, Myeloid, Time Factors, Transplantation Conditioning, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Kaplan-Meier Estimate, Gastroenterology, 0302 clinical medicine, HLA Antigens, Recurrence, Risk Factors, Bone Marrow Transplantation, Histocompatibility Testing, Total body irradiation, Middle Aged, 3. Good health, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Histocompatibility, Female, France, Unrelated Donors, Immunosuppressive Agents, Whole-Body Irradiation, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Busulfan, Antilymphocyte Serum, Proportional Hazards Models, Retrospective Studies, Transplantation, Peripheral Blood Stem Cell Transplantation, Chi-Square Distribution, [ SDV ] Life Sciences [q-bio], Thymoglobulin, business.industry, Myeloablative Agonists, medicine.disease, Myelodysplastic Syndromes, Immunology, Chronic Disease, Multivariate Analysis, Bone marrow, Dose Fractionation, Radiation, business, 030215 immunology
Abstract: International audience; BACKGROUND: The impact of antithymocyte globulin (ATG) in the setting of a myeloablative conditioning transplantation remains controversial, especially when using bone marrow (BM) as the stem cell source. METHODS: We therefore conducted a retrospective analysis to investigate the impact of ATG in patients with acute myeloid leukemia or myelodysplastic syndrome receiving myeloablative conditioning followed by a matched 10 of 10 unrelated donor transplant from BM or peripheral blood stem cells (PBSCs). Our study included 356 patients conditioned with cyclophosphamide associated with fractionated total body irradiation or busulfan. RESULTS: Median follow-up was 17.6 months (range, 0-156). The ATG and PBSCs were the only variables that independently decreased the cumulative incidence (CI) of chronic graft-versus-host disease (GvHD) (hazards ratio [HR], 0.4; 95% CI, 0.21-0.73; P \textless 0.01; and HR, 0.53; 95% CI, 0.30-0.90; P = 0.02, respectively). The ATG had no impact on overall survival, disease-free survival, relapse, and nonrelapse mortality. In the PBSC group (n = 139), ATG was associated with a lower CI of both grades III to IV acute GvHD (HR, 0.17; 95% CI, 0.03-0.91; P = 0.04), chronic GvHD (HR, 0.31; 95% CI, 0.11-0.87; P = 0.03), and GvHD-free/relapse-free survival (HR, 0.48; 95% CI, 0.29-0.80; P \textless 0.01), whereas these correlations were not significant in the group of patients (n = 217) receiving BM (HR, 0.36; 95% CI, 0.11-1.93; P = 0.06 for grade III-IV acute GvHD; HR, 0.49; 95% CI, 0.22-1.06; P = 0.08 for chronic GvHD; and HR, 0.69; 95% CI, 0.46-1.01; P = 0.06 for GvHD-free/relapse-free survival). CONCLUSIONS: Although our results confirm the recommendation for ATG to be added after PBSC transplantation, no obvious benefit was identified using this approach in the setting of BM transplantation. Only prospective studies may yield definitive answers to this question
Published: 2016
Full Text: View/download PDF

45. Late Complications and Quality of Life after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation

Author: Noel Milpied, Aline Clavert, Philippe Moreau, Steven Le Gouill, Béatrice Mahé, Thierry Guillaume, Harousseau Jl, Eolia Brissot, Florent Malard, Thomas Gastinne, Jacques Delaunay, Patrice Chevallier, Viviane Dubruille, Zinaida Peric, Nicolas Blin, Mohamad Mohty, Bernardo, Elizabeth, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Lung Diseases, Male, Quality of life, medicine.medical_specialty, Transplantation Conditioning, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Young Adult, 03 medical and health sciences, 0302 clinical medicine, conditioning, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surveys and Questionnaires, Internal medicine, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Survivors, Aged, Cause of death, Reduced-intensity, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Late effect, Cancer, Neoplasms, Second Primary, Hematology, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Surgery, Natural history, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Long-term effects, medicine.symptom, Reduced-intensity conditioning, business, Follow-Up Studies, 030215 immunology
Abstract: International audience; Late complications (LC) and quality of life (QOL) were analyzed in 110 adult patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) and were alive for more than 2 years after allo-SCT. Overall survival of these patients was 93% (95% confidence interval [CI], 88% to 99%) and 81% (95% CI, 71% to 94%) at 5 and 10 years, respectively. The primary cause of death was a recurrence of primary malignancy. With a median follow-up of 4.6 years (range, 2 to 12.1), chronic graft-versus-host disease (cGVHD) was the most prevalent late effect, with a cumulative incidence of 66% (95% CI, 57% to 74%) at 10 years. Car-diovascular complications were the most prevalent LC with a cumulative incidence of 47% (95% CI, 35% to 59%), followed by pulmonary complications with a cumulative incidence of 33% (95% CI, 21% to 46%) and renal impairment with a cumulative incidence of 34% (95% CI, 25% to 43%) at 10 years. Secondary malignancies occurred with a cumulative incidence of 11% (95% CI, 5% to 20%) at 10 years. In this series, 61 patients (55%) responded to QOL survey. With the use of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 and Functional Assessment of Cancer Therapy–Bone Marrow Transplant questionnaires , most of the patients reported good to excellent QOL and patients with cGVHD had significantly lower QOL than patients without cGVHD. In conclusion, QOL after RIC is comparable to that seen after myeloablative conditioning, while the natural history of LC after RIC appears to be different from that described in the standard myeloablative setting, warranting further research in this field.
Published: 2016
Full Text: View/download PDF

46. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study

Author: Patrice Chevallier, Carlos Graux, Vahid Asnafi, Anne Moreau, Thomas Vermeulin, Jacques Benichou, Gilles Salles, Stephanie Seris, Josette Brière, Norbert Ifrah, Aline Tanguy-Schmidt, Stéphane Leprêtre, Elizabeth Macintyre, Marie-Christine Béné, Jean-Michel Picquenot, Aurore Touzart, Serge Bologna, Reda Bouabdallah, Valérie Tallon-Simon, Françoise Huguet, Emmanuel Raffoux, Thierry Lamy, Hervé Dombret, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Charles Nicolle [Tunis], Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), HEMATOLOGIE, CRLCC Henri Becquerel, Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie clinique, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Purpan ( CHU Purpan ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Cliniques Universitaires UCL de Mont-Godinne, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), The study was supported by a grant from the French Ministry of Health (Projet Hospitalier de Recherche Clinique of France [PHRC 2003 No. 13-2]). The Macintyre laboratory was supported by the Fondation de France, the Association de Recherche sur le Cancer, Cent pour Sang la Vie, and the Société Française des Cancers de l’Enfant. CHUGAI PHARMA France provided technical and financialsupport., Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de biostatistiques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Université Toulouse III - Paul Sabatier ( UPS ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Bernardo, Elizabeth
Subjects: Male, Cancer Research, F-Box-WD Repeat-Containing Protein 7, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Phases of clinical research, Cell Cycle Proteins, Hematopoietic stem cell transplantation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Central Nervous System Diseases, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Young adult, Receptor, Notch1, Prospective cohort study, Hematopoietic Stem Cell Transplantation, Induction Chemotherapy, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, Ubiquitin-Protein Ligases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, medicine, Humans, Survival rate, [ SDV ] Life Sciences [q-bio], L-Lactate Dehydrogenase, business.industry, F-Box Proteins, Lymphoblastic lymphoma, PTEN Phosphohydrolase, Induction chemotherapy, medicine.disease, Surgery, Consolidation Chemotherapy, ras Proteins, business, 030215 immunology
Abstract: Purpose This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). Patients and Methods This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. Results The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. Conclusion In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.
Published: 2016
Full Text: View/download PDF

47. Radioimmunotherapy for Treatment of Acute Leukemia

Author: Patrice Chevallier, Marie Mougin, Michel Chérel, Mickaël Bourgeois, François Guérard, Alain Faivre-Chauvet, Françoise Kraeber-Bodéré, Joëlle Gaschet, Clément Bailly, T. Eugène, Caroline Bodet-Milin, Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'Hématologie, Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID
Subjects: 0301 basic medicine, medicine.drug_class, medicine.medical_treatment, CD33, [SDV.CAN]Life Sciences [q-bio]/Cancer, Monoclonal antibody, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigens, CD, hemic and lymphatic diseases, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Pretargeting, Acute leukemia, Leukemia, business.industry, Myeloid leukemia, Immunotherapy, Radioimmunotherapy, 3. Good health, Haematopoiesis, 030104 developmental biology, 030220 oncology & carcinogenesis, Acute Disease, Immunology, business
Abstract: International audience; Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmuno-therapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL. Semin Nucl Med 46:135-146 C
Published: 2016
Full Text: View/download PDF

48. Prevention of Venous Thrombotic Events in Adult Patients with Acute Lymphoblastic Leukemia Treated in a Pediatric-Inspired Protocol - a Graall Study

Author: Emmanuelle Tavernier, Denis Caillot, Yves Chalandon, Sylvain Chantepie, Françoise Huguet, Thomas Pabst, Norbert Ifrah, Corentin Orvain, Nicolas Boissel, Hervé Dombret, Patrice Chevallier, Marie Balsat, Mathilde Hunault-Berger, Véronique Lhéritier, Jamile Frayfer, Victoria Cacheux, Noémie de Gunzburg, Jean-Pierre Marolleau, Caroline Bonmati, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'hématologie, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Amiens-Picardie, Inselspital Bern, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier de Meaux, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), PRES Université Nantes Angers Le Mans (UNAM), and DESSAIVRE, Louise
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, business.industry, Cell Biology, Hematology, Odds ratio, medicine.disease, Thrombosis, Surgery, Discontinuation, Pulmonary embolism, Transplantation, [SDV] Life Sciences [q-bio], Venous thrombosis, Platelet transfusion, 030220 oncology & carcinogenesis, Fresh frozen plasma, business
Abstract: Background: Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP) and subsequent antithrombine (AT) deficiency. Previous reports showed that patients with venous thrombotic events (VTE) have a lower event-free survival that may be due to early discontinuation of L-ASP. It has been suggested that AT replacement could decrease the rate of thrombosis and prevent L-ASP discontinuation. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Methods: All patients received a 5-drug induction therapy with 8 native E. Coli-ASP intravenous injections (6,000 UI/m2/injection). Patients in complete remission (CR) received two consolidation courses each containing two L-ASP intravenous injections (10000 UI/m2/injection). All patients in persistent CR for whom allogeneic stem cell transplantation was not indicated in first CR received a late intensification with the same drugs as in the induction course, followed by the repetition of one consolidation course. Platelet transfusion support was recommended for platelets below 20 x 109/L, fresh frozen plasma (FFP) or fibrinogen concentrates were recommended if fibrinogen levels fell below 0.5 g/L, and AT concentrate substitution therapy was recommended in order to maintain AT levels above 60%. Prophylactic heparin was recommended during induction and late intensification. All cases of VTE were identified prospectively by clinical signs and confirmed by radiological imaging based on institutional guidelines. Results: Between 2006 and 2014, 787 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 14.4% (113 VTEs in 110 patients). VTEs included 72 (64%) deep vein thromboses (DVT), with one third in the lower limb and two thirds in the upper limb, 32 (28%) cerebral venous thrombosis (CVT), and 13 (12%) pulmonary embolism (PE). No disease characteristic was associated with a higher risk of thrombosis. Patients with DVT and/or PE were older (median age of 40 versus 38 for those with CVT versus 35 for those without VTE, p=0.04), had a higher BMI (median BMI of 26 versus 23 for those with CVT and 24 for those without VTE, p=0.01), and had a higher platelet count at diagnosis (median platelet count of 100 G/l versus 84 G/l for those with CVT versus 68 G/l for those without VTE, p=0.06) whereas patients with CVT had higher hemoglobin levels (median hemoglobin level of 11.7 g/dl versus 10.1 g/dl for those with DVT/PE versus 10.2 g/dl for those without VTE, p=0.03). Sixty-seven percent of VTEs occurred during induction therapy. Other VTEs occurred as follows: 17 (15%) during consolidation phase 1 (688 patients), 4 (4%) during consolidation phase 2 (537 patients), 9 (8%) during late intensification (356 patients), and 7 (6%) in 335 during consolidation phase 3 (335 patients). The type of thrombosis was different according to treatment phase as most CVT occurred during induction therapy (29 versus 3 CVTs during subsequent phases of treatment, p=0.003). During induction therapy, patients with VTE were more likely to have received heparin prophylaxis (82% versus 60% for those without VTE, odds ratio (OR) 1.8, p=0.06) and fibrinogen prophylaxis (14% versus 8% for those without VTE, OR 2, p=0.05) whereas they received less AT prophylaxis (82% versus 88% for those without VTE, OR 0.5, p=0.05). Patients with VTE received less L-ASP infusions during induction therapy (median number of 7 versus 8 injections for those without VTE, p Conclusion: In ALL patients receiving L-ASP therapy, appropriate AT prophylaxis was associated with less VTE and should be used extensively. Maintaining higher AT levels in patients at increased risk for VTE should be evaluated. L-ASP can be reintroduced in patients who experienced VTE during induction as none had thrombotic recurrence. Fibrinogen concentrates may increase the risk of thrombosis and should be restricted to patients with hemorrhage. Disclosures Dombret: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.
Published: 2016
Full Text: View/download PDF

49. Allogeneic stem cell transplantation for patients with mantle cell lymphoma who failed autologous stem cell transplantation: a national survey of the SFGM-TC

Author: Lucie Oberic, Gaelle Guillerm, Olivier Hermine, Patrice Chevallier, S. Le Gouill, O. Tournilhac, Benoit Tessoulin, Gérard Socié, H. Tilly, Tony Marchand, Jordan Gauthier, Jérôme Cornillon, N. Maillard, Stephane Girault, Norbert Ifrah, Emmanuel Bachy, Didier Blaise, Sylvain Carras, R. Tabrizi, Patrice Ceballos, Oumedaly Reman, Christophe Leux, Etienne Daguindau, M. Mohty, Sylvain Choquet, Bernardo, Elizabeth, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Service d'Hématologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Clinical Haematology, CHU Hôtel-Dieu, Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service hématologie Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie et Thérapie Cellulaire, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Départment d'Hématologie, Centre National de la Recherche Scientifique (CNRS), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Epidémiologie et Biostatistique [Nantes], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymphoma, Mantle-Cell, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, Surveys and Questionnaires, hemic and lymphatic diseases, medicine, Humans, Transplantation, Homologous, Progenitor cell, Survival analysis, Aged, Salvage Therapy, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Surgery, Graft-versus-host disease, surgical procedures, operative, 030220 oncology & carcinogenesis, Female, Rituximab, Mantle cell lymphoma, France, Stem cell, business, therapeutics, human activities, 030215 immunology, medicine.drug
Abstract: International audience; Poly-chemotherapy plus rituximab followed by autologous stem cell transplantation (auto-SCT) is standard care for untreated young patients with mantle cell lymphoma (MCL). Despite this intensive treatment, transplant patients remain highly susceptible to relapse over time. The French SFGM-TC performed a national survey on reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) for fit relapsed/refractory patients who failed after auto-SCT (n=106). Median times of relapse after auto-SCT, and from auto-SCT to RIC-allo-SCT were 28 months and 3.6 years, respectively. Sixty per cent of patients received at least three lines of treatment before RIC-allo-SCT. Conditioning regimens for RIC-allo-SCT were heterogeneous. Twenty patients experienced grade III/IV aGvHD, extensive cGvHD was reported in 28 cases. Median follow-up after RIC-allo-SCT was 45 months. Median PFS after RIC-allo-SCT was 30.1 months and median overall survival was 62 months. Treatment-related mortality (TRM) at 1 year and 3 years were estimated at 28% and 32%, respectively. A total of 52 patients died; major causes of death were related to toxicity (n=34) and MCL (n=11). Patients in good response before RIC-allo-SCT experienced a better PFS and OS. Our work highlights the need for new RIC-allo-SCT MCL-tailored approaches to reduce TRM, and early and late relapse.
Published: 2016
Full Text: View/download PDF

50. Higher Early Monocyte and Total Lymphocyte Counts Are Associated with Better Overall Survival after Standard Total Body Irradiation, Cyclophosphamide, and Fludarabine Reduced-Intensity Conditioning Double Umbilical Cord Blood Allogeneic Stem Cell Transplantation in Adults

Author: Jacques Delaunay, Loïc Campion, Alix Duquesne, Steven Le Gouill, Amandine Le Bourgeois, Thierry Guillaume, Mohamad Mohty, Philippe Moreau, Patrice Chevallier, Pierre Peterlin, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Etablissement Français du Sang [Nantes], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, and Bernardo, Elizabeth
Subjects: Male, Transplantation Conditioning, Lymphocyte, Umbilical cord, Gastroenterology, Monocytes, Leukocyte Count, 0302 clinical medicine, Granulocyte Colony-Stimulating Factor, Medicine, Lymphocytes, Immune recovery, Hazard ratio, Graft Survival, Hematology, Total body irradiation, Middle Aged, 3. Good health, Fludarabine, Allogeneic stem cell, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Cord Blood Stem Cell Transplantation, Vidarabine, Whole-Body Irradiation, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Double umbilical cord blood, Humans, Transplantation, Homologous, Adults, Lymphocyte Count, Aged, business.industry, Monocyte, Hematological recovery, Surgery, Transplantation, Reduced-intensity conditioning, regimen, business, 030215 immunology, transplantation
Abstract: International audience; This single-center retrospective study aimed to report the impact of early hematopoietic and immune recoveries after a standard total body irradiation, cyclophosphamide, and fludarabine (TCF) reduced-intensity conditioning (RIC) regimen for double umbilical cord blood (dUCB) allogeneic stem cell transplantation (allo-SCT) in adults. We analyzed 47 consecutive patients older than 17 years who engrafted after a dUCB TCF allo-SCT performed between January 2006 and April 2013 in our department. Median times for neutrophil and platelet recoveries were 17 (range, 6 to 59) and 37 days (range, 0 to 164), respectively. The 3-year overall (OS) and disease-free survivals, relapse incidence, and nonrelapse mortality were 65.7%, 57.2%, 27.1%, and 19%, respectively. In multivariate analysis, higher day þ30 monocyte (!615/mm 3 ; hazard ratio [HR], .04; 95% confidence interval [CI], .004 to .36; P < .01) and day þ42 lymphocyte (!395/mm 3 ; HR, .16; 95% CI, .03 to .78; P ¼ .02) counts were independently associated with better OS. These results suggest that early higher he-matopoietic and immune recovery is predictive of survival after dUCB TCF RIC allo-SCT in adults. Factors other than granulocyte colonyestimulating factor, which was used in all cases, favoring expansion of monocytes or lymphocytes, should be tested in the future as part of the UCB transplantation procedure.
Published: 2016
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Database

62 results on '"Patrice Chevallier"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources