40 results on '"Henrik Sengeloev"'
Search Results
2. Validation of the Transplant Conditioning Intensity (TCI) Score for Allogeneic Hematopoietic Cell Transplantation
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Alexandros Spyridonidis, Myriam Labopin, Tobias Gedde-Dahl, Arnold Ganser, Matthias Stelljes, Charles Craddock, Eva Maria Wagner, Jurjen Versluis, Thomas Schroeder, Igor Wolfgang Blau, Gerald Wulf, Peter Dreger, Gitte Olesen, Henrik Sengeloev, Nicolaus Kröger, Victoria Potter, Edouard Forcade, Jakob Passweg, Régis Peffault de Latour, Johan Maertens, Keith Wilson, Jean-Henri Bourhis, Bipin Savani, Fabio Ciceri, Arnon Nagler, and Mohamad Mohty
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
3. Gvhd Prophylaxis Incorporating Methotrexate in Allo-HCT for Chronic Myeloid Malignancies and sAML: A Retrospective Analysis from the Cmwp of the EBMT
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Thomas Luft, Luuk Gras, Linda Kostner, Nicolaus Kröger, Thomas Schroeder, Uwe Platzbecker, Johannes Schetelig, Régis Peffault de Latour, Matthias Stelljes, Henrik Sengeloev, Arnold Ganser, Igor Wolfgang Blau, Peter Dreger, Ibrahim Yakoub-Agha, Johan Maertens, Urpu Salmenniemi, Wolfgang Bethge, Stephan Mielke, Guido Kobbe, Anastasia Pouli, Liesbeth C. de Wreede, Kavita Raj, Joanna Drozd-Sokolowska, Donal P. McLornan, and Marie Robin
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
4. Data from Impact of Donor Type in Patients with AML Given Allogeneic Hematopoietic Cell Transplantation After Low-Dose TBI-Based Regimen
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Arnon Nagler, Mohamad Mohty, Eliane Gluckman, Bipin N. Savani, Didier Blaise, Noel Milpied, Harry C. Schouten, Marco R. De Groot, Dietger Niederwieser, Henrik Sengeloev, Ellen Meijer, Jan J. Cornelissen, Annalisa Ruggeri, Myriam Labopin, and Frédéric Baron
- Abstract
Purpose: We assessed the impact of donor type in acute myeloid leukemia (AML) patients transplanted with 2 Gy total body irradiation (TBI)-based nonmyeloablative conditioning regimen.Patients and Methods: Data from 1,715 adult patients, with AML in CR1 or CR2 were included in this retrospective survey.Results: Donors consisted either of HLA-matched sibling donors (MSD, n = 701), 10/10 HLA-matched unrelated donors (MUD, n = 611), HLA-haploidentical donors (haplo, n = 112) or single or double umbilical cord bloods (CBT, n = 291). Chronic graft-versus-host disease (GVHD) was less frequent in CBT (28%) and in haplo (30%) patients than in MSD (50%) and MUD (51%) recipients (P < 0.001). Two-year incidence of relapse was 32%, 30%, 34%, and 34% in MSD, MUD, CBT and haplo patients, respectively (P = 0.7). Two-year overall (OS) and GVHD-free relapse-free survival (GRFS) were 59% and 29% in MSD patients, 56% and 39% in CBT recipients, 53% and 23% in MUD recipients, and 43% and 37% in haplo patients, respectively. In multivariate analyses, MUD patients had lower GRFS than MSD patients beyond day 100 (HR 1.3, P = 0.001) while CBT was associated with a better GRFS than MSD beyond day 100 (HR 0.6, P = 0.002).Conclusions: In this large cohort of AML patients transplanted following low-dose TBI-based conditioning, the relapse incidence was not affected by donor type suggesting that the intensity of GVL effects might be comparable with these four transplant approaches. Furthermore, CBT was associated with better GRFS beyond day 100 than MSD while the opposite was observed for MUD. Clin Cancer Res; 24(12); 2794–803. ©2018 AACR.
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- 2023
5. The European landscape on allogeneic haematopoeietic cell transplantation in Chronic Lymphocytic Leukaemia between 2009 and 2019: a perspective from the Chronic Malignancies Working Party of the EBMT
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Olivier Tournilhac, Michel van Gelder, Dirk-Jan Eikema, Nienke Zinger, Peter Dreger, Martin Bornhäuser, Vladan Vucinic, Christof Scheid, Jan J. Cornelissen, Thomas Schroeder, Pavel Jindra, Henrik Sengeloev, Stephanie Nguyen Quoc, Matthias Stelljes, Igor Wolfgang Blau, Jiri Mayer, Shankara Paneesha, Patrice Chevallier, Edouard Forcade, Nicolaus Kröger, Didier Blaise, John Gribben, Bendt Nielsen, Jan-Erik Johansson, Charalampia Kyriakou, Yves Beguin, Pietro Pioltelli, Antònia Sampol, Donal P. McLornan, Johannes Schetelig, Patrick J. Hayden, Ibrahim Yakoub-Agha, and Hematology
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Transplantation ,Medizin ,Hematology ,CLL - Abstract
Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009–2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2–3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness.
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- 2023
6. Validation of the Transplant Conditioning Intensity (TCI) Index for Allogeneic Hematopoietic Cell Transplantation
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Alexandros Spyridonidis, Myriam Labopin, Tobias Gedde-Dahl, Arnold Ganser, Matthias Stelljes, Charles Craddock, Eva Wagner-Drouet, Jurjen Versluis, thomas schroeder, Igor-Wolfgang Blau, Gerald Wulf, Peter Dreger, Gitte Olesen, Henrik Sengeloev, Nicolaus Kroeger, Victoria Potter, Edouard Forcade, Jakob Passweg, Regis Peffault de Latour, Johan Maertens, Keith Wilson, Jean Henri Bourhis, Jürgen Finke, Eolia Brissot, Ali Bazarbachi, Sebastian Giebel, Bipin N. Savani, Arnon Nagler, Fabio Ciceri, and Mohamad Mohty
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The intensity of the conditioning regimen given before allogeneic hematopoietic cell transplantation (allo-HCT) can vary substantially. To confirm the ability of the recently developed transplant conditioning intensity (TCI) score to stratify the preparative regimens of allo-HCT, we used an independent and contemporary patient cohort of 4060 transplant recipients with acute myeloid leukemia meeting inclusion criteria from the discovery study (allo-HCT in first complete remission, matched donor), but who were allografted in a more recent period (2018–2021) and were one decade older (55–75 years, median 63.4 years), we assigned them to a TCI category (low n = 1934, 48%; intermediate n = 1948, 48%, high n = 178, 4%) according to the calculated TCI score ([1–2], [2.5–3.5], [4–6], respectively), and examined the validity of the TCI category in predicting early non-relapse mortality (NRM), 2-year NRM and relapse (REL). In the unadjusted comparison, the TCI index provided a highly significant risk stratification for d100 and d180 NRM, NRM and REL risk. In the multivariate analysis adjusted for significant variables, there was an independent strong association of TCI with early NRM, NRM and REL. In summary, we confirm in contemporary treated patients that TCI reflects the conditioning regimen related morbidity and anti-leukemic efficacy highly satisfactorily and across other established prognostic factors. TCI has all the features to be used as a well-defined, easy calculated and reproducible tool to define and measure intensity of the preparative regimen.
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- 2023
7. Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT
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Edouard Forcade, Sylvie Chevret, Jürgen Finke, Gerhard Ehninger, Francis Ayuk, Dietrich Beelen, Linda Koster, Arnold Ganser, Liisa Volin, Henrik Sengeloev, Mauricette Michallet, Johanna Tischer, Pavel Jindra, Maria Jesús Pascual Cascon, Yener Koc, Mutlu Arat, Agnieszka Tomaszewska, Patrick Hayden, Theo de Witte, Ibrahim Yakoub-Agha, Nicolaus Kröger, and Marie Robin
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Transplantation ,Transplantation Conditioning ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,T-Lymphocytes ,Hematopoietic Stem Cell Transplantation ,Medizin ,Graft vs Host Disease ,Hematology ,Treatment Outcome ,Recurrence ,Myelodysplastic Syndromes ,Neoplasms ,Humans ,Transplantation, Homologous ,Registries ,Alemtuzumab ,Retrospective Studies - Abstract
Item does not contain fulltext While in vivo T-cell depletion (TCD) is widely used, its benefit in patients with MDS still remains a matter of debate. This study evaluates the impact of TCD on outcomes, and compares ATG and alemtuzumab, in patients with MDS. 1284 patients from the EBMT registry were included in this study with 470 patients in the no-TCD group and 814 in the TCD group (alemtuzumab N = 168; ATG N = 646). At 6 months, aGVHD III-IV cumulative incidences (CI) for no-TCD, ATG or alemtuzumab groups were 13% vs 14% vs 11% (ns), respectively. At 5 years, CI of chronic GVHD were 64% vs 52% vs 51% (p
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- 2022
8. Transplantation for Congenital Sideroblastic Anaemia Is Feasible and Offers Outcomes Comparable to Other Transfusion Dependent Anaemias. a Joint Retrospective Study of the Paediatric Diseases and Severe Aplastic Anaemia Working Parties (PDWP/SAAWP) of EBMT
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Régis Peffault de Latour, Carlo Dufour, Miguel Angel Diaz, Vassiliki Kitra-Roussou, John Moppett, Antonio M. Risitano, Abdelghani Tbakhi, John G. Gribben, Antonio Martinez, Tessa Kerre, Tobias Gedde-Dahl, Henrik Sengeloev, Muhlis Cem Ar, Josu de la Fuente, Cristina Díaz de Heredia, Paul Bosman, Mohamed Salaheldin Mohamed, Dominique Bron, Stig Lenhoff, José M. Moraleda, Hendrik Veelken, Giuseppe Visani, Selim Corbacioglu, Peter J. Shaw, Amal Al-Seraihy, Brenda Gibson, Dirk-Jan Eikema, Rupert Handgretinger, Estelle Verburgh, and Robert Wynn
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Pediatrics ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,education ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Treosulfan ,medicine.disease ,Biochemistry ,Fludarabine ,Transplantation ,Regimen ,medicine ,Alemtuzumab ,Reticulocytopenia ,business ,health care economics and organizations ,medicine.drug - Abstract
Congenital sideroblastic anaemias (CSA) are a rare group of disorders characterized by the presence of pathologic iron deposits within the mitochondria of erythroid precursors (ring sideroblasts) in the bone marrow due to heterogenous germline mutations leading to defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Patients present with anaemia and relative reticulocytopenia, and systemic iron overload secondary to chronic ineffective erythropoiesis, leading to end-organ damage. The disease is heterogenous underlying the genetic variability and the variable response to treatment. Although a number of CSA patients have received a bone marrow transplant, the outcomes and toxicities are not known. This status makes it very difficult to understand the role of BMT in the management of CSA. A search in the EBMT database identified 28 patients receiving a HSCT for CSA between 1998 to 2018 by 24 participating centres. The median year of transplantation was 2014 (IQR 2004-2016). The distribution was equal between males (n=14) and females (n=14). The median age at transplantation was 7 years of age (3-10 years). Fifteen patients had a sibling HSCT (88%), one a family matched donor HSCT (6%) and one an unrelated matched (6%), the type of transplant being unknown in others (n=11). The source of stem cells was bone marrow in 20 cases (74%), peripheral blood in 4 cases (15%), cord blood in 2 (7%) and combined bone marrow and cord in one (4%). Five cases had a Bu/Cy based conditioning regimen, 4 had Bu/fludarabine based regimen and three fludarabine/treosulfan based conditioning with the rest having a variety of approaches. Eighty-six percent of cases had serotherapy with ATG or alemtuzumab. The median follow-up was 31.6 months (95% CI, 12.2-74.1%). The overall survival at 12 and 24 months was 88% (76-100) and 82% (66-99), respectively (figure 1). The median neutrophil engraftment was 18 (15-21) days and platelet engraftment >20 x 109/L was 29 (20-51) days, with a graft failure incidence of 7% (0-17) at 12 months. Two patients suffered from VOD. There were four deaths, three of which were related to transplant complications. The event free survival (survival without graft failure, relapse and second transplant) at 12 and 24 months was 85% (72-99) (figure 2). Six patients developed acute GvHD grade II and one case grade III; giving a grade II/III incidence of 28% (10-46). There was one case of limited and one of chronic GvHD, giving an incidence of 11% (0-26%) at 12 months and 24 months. In conclusion, whilst HSCT for CSA is a rare occurrence, these data demonstrate that HSCT for this condition is feasible and the outcomes are in keeping with those obtained for transplantation for transfusion dependent anaemias during the same time-period. Disclosures Handgretinger: Amgen: Honoraria. Moraleda:Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel Expenses; Sandoz: Consultancy, Other: Travel Expenses; Takeda: Consultancy, Other: Travel Expenses. Risitano:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Speakers Bureau. Peffault De Latour:Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.
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- 2020
9. Comparison of long-term outcome for AML patients alive free of disease 2 years after allogeneic hematopoietic cell transplantation with umbilical cord blood versus unrelated donor: a study from the ALWP of the EBMT
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Martin Bornhäuser, Gérard Socié, Maud Ngoya, Frédéric Baron, Arnold Ganser, Henrik Sengeloev, Annalisa Ruggeri, Hans Christian Reinhardt, Jan J. Cornelissen, Edouard Forcade, Mohamad Mohty, Arnon Nagler, Myriam Labopin, Nicolaus Kröger, Didier Blaise, Thomas Valerius, GIGA [Université Liège], Université de Liège, Centre Hospitalier Universitaire de Liège (CHU-Liège), CEREST-TC [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-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 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), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hannover Medical School [Hannover] (MHH), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], National University Hospital, Rigshospitalet, Copenhagen, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Medizinische Klinik und Poliklinik I [Dresden, Germany], Universitätsklinikum 'Carl Gustav Carus' Dresden, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), IRCCS San Raffaele Scientific Institute [Milan, Italie], Chaim Sheba Medical Center, and Hematology
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Male ,medicine.medical_specialty ,Multivariate analysis ,Transplantation Conditioning ,Medizin ,Graft vs Host Disease ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Disease ,Umbilical cord ,Unrelated Donor ,Internal medicine ,Medicine ,Humans ,Retrospective Studies ,Transplantation ,Hematopoietic cell ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Fetal Blood ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Female ,business ,Unrelated Donors - Abstract
International audience; Since cord blood transplantation (CBT) has been associated with high graft-versus-leukemia effects and a low incidence of chronic graft-versus-host disease (GVHD), we hypothesized that long-term outcomes might be better in CBT patients than in those given grafts from unrelated donors (UD). Therefore, we performed a landmark study comparing long-term outcomes in acute myeloid leukemia (AML) patients alive and disease-free 2 years after transplantation who received grafts from either CBT or UD. A total of 364 CBT recipients, 2648 UD 10/10 patients and 681 patients given grafts from UD 9/10 were included. Median follow-up was 6.0 years. Five-year leukemia-free survival (LFS) from transplantation was 86% in CBT patients, 84% in UD 10/10 patients (P = 0.36) and 84% in UD 9/10 patients (P = 0.86). On multivariate analysis, donor type had no impact on LFS. Similarly, no impact of donor type was observed on relapse incidence or non-relapse mortality. Factors associated with poorer LFS on multivariate analysis included higher age at transplantation (P < 0.001), male gender (P < 0.001), second complete remission (CR2) versus CR1 (P = 0.05), secondary AML (P = 0.01), antecedent of chronic GVHD (P < 0.001) and poor-risk cytogenetics (P = 0.01). In conclusion, our study shows that long-term outcome for AML patients in CR two years after transplantation is not impacted by donor type.
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- 2021
10. Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia Older Than 50 Years: A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Dietrich W. Beelen, Arnon Nagler, Michael Byrne, Myriam Labopin, Didier Blaise, Bipin N. Savani, Dietger Niederwieser, Arnold Ganser, Reza Tabrizi, Henrik Sengeloev, Jürgen Finke, Mohamad Mohty, Jan J. Cornelissen, Gerhard Ehninger, Avichai Shimoni, Liisa Volin, Hematology, HUS Comprehensive Cancer Center, and Department of Oncology
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Male ,Transplantation Conditioning ,Graft vs Host Disease ,0302 clinical medicine ,AML ,immune system diseases ,hemic and lymphatic diseases ,Societies, Medical ,SUPERIOR ,Acute leukemia ,IDENTICAL SIBLINGS ,Marrow transplantation ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Middle Aged ,3. Good health ,Europe ,Survival Rate ,Leukemia ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,030220 oncology & carcinogenesis ,SURVIVAL ,Female ,Stem cell ,Unrelated Donors ,REDUCED-INTENSITY ,long-term outcome ,Unrelated donor ,medicine.medical_specialty ,Sibling ,3122 Cancers ,Disease-Free Survival ,03 medical and health sciences ,CONDITIONING REGIMEN ,Internal medicine ,parasitic diseases ,medicine ,Humans ,In patient ,Aged ,Retrospective Studies ,Transplantation ,Acute myeloid leukemia ,business.industry ,MORTALITY ,Siblings ,ADULTS ,medicine.disease ,Allogeneic stem cell transplantation ,LATE DEATHS ,business ,030215 immunology - Abstract
Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P = .005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P.001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P = .78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P = .30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P = .0001) or CR2 (HR, 1.51; P = .02) compared with CR1, female recipients (HR, 0.71; P = .006), adverse cytogenetics (HR, 2.52; P = .01), and prior graft-versus-host disease (HR, 1.31; P = .04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P = .97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P = .15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types.
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- 2019
11. Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma-type Richter syndrome
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Yue Chen, Amelia Langston, Silvy Lachance, Joseph P. McGuirk, Amer Assal, Matthew Greenwood, Alex F. Herrera, Samantha Jaglowski, Mehdi Hamadani, Henrik Sengeloev, Adrienne A. Phillips, Mitchell E. Horwitz, Carlos Litovich, Richard T. Maziarz, Mohammad A. H. Mian, Robert K. Stuart, Kevin Rakszawski, Nosha Farhadfar, Theresa Hahn, Ruthee-Lu Bayer, Bassam Mattar, Mohamed A. Kharfan-Dabaja, Shalini Shenoy, Qaiser Bashir, Zachariah DeFilipp, Caron A. Jacobson, Melanie Coleman, Craig S. Sauter, Sunita Nathan, and Kwang Woo Ahn
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Chronic lymphocytic leukemia ,Aggressive lymphoma ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,Medicine ,Humans ,Not evaluated ,Transplantation ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphoma ,surgical procedures, operative ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma - Abstract
Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), which is associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy; thus, consolidation with hematopoietic cell transplantation (HCT) has been used, with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel targeted therapy of CLL/SLL. We performed a Center for International Blood and Transplant Research registry study evaluating outcomes after autologous HCT (auto-HCT; n = 53) and allogeneic HCT (allo-HCT; n = 118) in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response (CR) at HCT relative to allo-HCT recipients (66% vs 34%), whereas a higher proportion of allo-HCT recipients had 17p deletion (33% vs 7%) and had previously received novel agents (39% vs 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3-year PFS/OS, 66%/77% CR vs 43%/57% partial response vs 5%/15% resistant; P < .0001 for both), whereas cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.
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- 2021
12. C-Reactive Protein Levels at Diagnosis of Acute Graft-versus-Host Disease Predict Steroid-Refractory Disease, Treatment-Related Mortality, and Overall Survival after Allogeneic Hematopoietic Stem Cell Transplantation
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Ida Schiødt, Lia Minculescu, Henrik Sengeloev, Brian Kornblit, Lone Smidstrups Friis, Soeren Lykke Petersen, and Niels Smedegaard Andersen
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Male ,Lymphocyte ,medicine.medical_treatment ,Drug Resistance ,Graft vs Host Disease ,Disease ,Hematopoietic stem cell transplantation ,Graft-versus-host disease ,Gastroenterology ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,biology ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Allografts ,Survival Rate ,C-Reactive Protein ,surgical procedures, operative ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Acute Disease ,Allogeneic hematopoietic stem cell transplantation ,Female ,Steroids ,medicine.symptom ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Inflammation ,Disease-Free Survival ,C-reactive protein ,03 medical and health sciences ,Internal medicine ,White blood cell ,medicine ,Humans ,Aged ,Transplantation ,business.industry ,medicine.disease ,Infliximab ,Immunology ,biology.protein ,business ,030215 immunology - Abstract
Acute graft-versus-host disease (aGVHD) remains a cause of excessive morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Primary treatment consists of high-dose corticosteroids, but a small group of patients develop steroid-refractory disease, and their prognosis is especially poor. There is experimental evidence that coexisting inflammation aggravates aGVHD. Because C-reactive protein (CRP) is a systemic inflammatory marker, we aimed to investigate whether plasma CRP concentrations at the diagnosis of aGVHD can predict the risk of failing first-line therapy and developing steroid-refractory disease. We retrospectively studied 461 patients who underwent HSCT between 2010 and 2015. aGVHD grade II-IV was diagnosed in 148 patients (32%). CRP level and total white blood cell, lymphocyte, and neutrophil counts were available for all patients at the time of aGVHD diagnosis. According to local protocol, patients with failed response to high-dose steroid therapy (2 mg/kg) were treated with the TNF-α inhibitor infliximab and categorized as having steroid-refractory disease. Of 148 patients with grade II-IV aGVHD, 28 (19%) developed steroid-refractory disease. In these patients, plasma CRP concentration at diagnosis ranged between
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- 2018
13. Transplant Outcomes in Patients with Ph+ Chronic Myeloid Leukemia: Haploidentical Donors Compared to Matched Sibling Donors and Matched/Mismatched Unrelated Donors: A Retrospective Analysis from the EBMT Chronic Malignancies Working Party (EBMT-CMWP)
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Elena V. Morozova, Rose-Marie Hamladji, Jakob Passweg, Antonio Martinez, Arnold Ganser, Péter Reményi, Linda Koster, Luuk Gras, Andrew Clark, Marie Robin, Victoria Potter, Yves Chalandon, Jennifer Byrne, Urpu Salmenniemi, Patrick Hayden, Henrik Sengeloev, Mahmoud Aljurf, Ka Lung Wu, Kazimierz Hałaburda, Ge Junran, Francesco Onida, Jane F. Apperley, Stig Lenhoff, Charles Craddock, and Ibrahim Yakoub-Agha
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0303 health sciences ,medicine.medical_specialty ,business.industry ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Retrospective analysis ,In patient ,Sibling ,business ,030304 developmental biology ,030215 immunology - Abstract
Introduction: The role of allogeneic hematopoietic cell transplantation (allo-HCT) in Philadelphia-positive chronic myeloid leukemia (Ph+ CML) changed profoundly after the introduction of tyrosine kinase inhibitors (TKIs). Nevertheless, allo-HCT still represents the preferred treatment option for selected high-risk patients in Europe, with TKI resistance as the most common indication in first chronic phase (CP1). Reported survival outcomes for patients transplanted in CP1 with matched related (MRD), matched unrelated (MUD) and mismatched unrelated donors (MMUD) are generally good, but there are no published data on transplants from haploidentical donors (HD). In this retrospective study, we aimed to compare HD outcomes with those using MRD/MUD/MMUD. Patients and Methods: Patients who had received a first allo-HCT for Ph+ CML between 2012 and 2019 were selected from the EBMT database. Following the exclusion of patients transplanted using MRD, MUD, or MMUD and who received post-Cy GvHD prophylaxis, 1686 patients were included in the analysis. The impact of donor type on overall survival (OS) and relapse-free survival (RFS) was assessed using the Kaplan-Meier method; the cumulative incidence of relapse (REL) and non-relapse mortality (NRM) were estimated as competing events. Univariate comparisons were tested by log-rank or Gray's test, as appropriate. Cox proportional hazard models were applied to compare the risk of OS, RFS, REL and NRM in patients transplanted from MRD, MUD, MMUD and HD, adjusted for baseline disease and transplant characteristics, and to analyze the cause-specific hazard of NRM and REL. Two-sided p values of p Results: Overall, the median age at transplant was 46 years (range 18-74). 62% were male. The median interval from diagnosis to transplant was 17.5 months. Disease status at transplant was CP1 in 43%, CP2 or later in 27%, accelerated phase (AP) in 12%, and blast phase (BP) in 18%. Karnofsky Performance Status (KPS) was ≥90 in 78% of patients. Donor was MRD in 661 patients (39.2%), MUD in 677 (40.2%), MMUD in 212 (12.6%) and HD in 136 (8%). The stem cell source was peripheral blood (PB) in 84% (52% in HD, p20 x 10 9/L) engraftment was 25 days in HD, 14 days in MRD/ MUD and 15 days in MMUD transplants. 53% of patients were serologically CMV positive pre-transplant. The cumulative incidence of grade II-IV acute GvHD at Day +100 was 25%, 27%, 31% and 39% in HD, MRD, MUD and MMUD, respectively (p=0.008). Chronic GvHD at +60 months was observed in 36%, 49%, 40% and 48% in HD, MRD, MUD and MMUD transplants (p=0.006), respectively. With regard to transplant outcomes at 60 months in HD, MRD, MUD and MMUD, OS was 51%, 51%, 62% and 58% (p=0.22), RFS was 42%, 46%, 51% and 45% (p=0.03, Fig.1), REL was 37%, 35%, 28% and 31% (p=0.064), NRM was 21%, 20%, 21% and 24% (p=0.34), and GVHD-free/relapse-free survival (GRFS) was 23%, 22%, 32% and 26% (p Conclusions: Apart from confirming the stage of disease at transplant as being a major prognostic factor, this study identified a trend to better RFS and GRFS in patients with Ph+ CML transplanted using MUD when compared to MRD/HD/MMUD. These results should be interpreted with caution given the limited number of patients who had HD. Figure 1 Figure 1. Disclosures Byrne: Incyte: Honoraria. Apperley: Bristol Myers Squibb, Novartis: Honoraria, Speakers Bureau; Incyte, Pfizer: Honoraria, Research Funding, Speakers Bureau. Craddock: Novartis Pharmaceuticals: Other: Advisory Board ; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ganser: Novartis: Honoraria; Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria. Hayden: Amgen: Honoraria; Jansen, Takeda: Other: Travel, Accomodation, Expenses. Chalandon: Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Amgen: Other: Advisory Board; Incyte: Speakers Bureau; Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Gilead, Amgen, Jazz, Astra Zenec: Other: Travel EXpenses, Accomodation. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria.
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- 2021
14. Validation of Pre-Transplantation Plasma ST2 Levels As a Prognostic Marker of 1-Year Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplantation
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Brian Kornblit, Lone Smidstrup Friis, Henrik Sengeloev, Ida Schjødt, Søren Lykke Petersen, Frederikke Schierbeck, Lars Klingen Gjærde, Niels Smedegaard Andersen, and Sisse R. Ostrowski
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Transplantation ,Oncology ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Internal medicine ,Immunology ,medicine ,Nonrelapse mortality ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
Introduction: Accurate assessment of the risk of non-relapse mortality (NRM) is important for making the shared decision about treatment with allogeneic hematopoietic cell transplantation (allo-HCT). We have shown that the pre-transplantation plasma level of suppression of tumorigenicity 2 (ST2)-a protein that is released to the bloodstream upon inflammation, cellular stress and endothelial damage-was associated with NRM after myeloablative allo-HCT [Gjærde et al., ASH Annual Meeting 2020, abstract #1524]. In an expanded cohort of both myeloablative- and non-myeloablative conditioned patients, we aimed to validate the value of pre-transplant ST2 in predicting 1-year NRM after allo-HCT. Methods: Pre-transplantation plasma ST2 levels were measured by enzyme-linked immunosorbent assays in 374 adult patients who underwent allo-HCT at Rigshospitalet between July 2015 and December 2019 (Table 1), using stored plasma samples collected at a median (Q1, Q3) of 23 (21, 24) days before allo-HCT. All patients were followed-up for at least 1 year after transplant. NRM was defined as all deaths in relapse-free patients. Given our sample size and outcome proportion, we could include four parameters in a logistic regression model of 1-year NRM to avoid severe overfitting [Riley et al., BMJ, 2020]. Based on our current clinical risk assessment practice, we included age (linear), comorbidity index (HCT-CI [Sorror et al., Blood, 2005], linear) and conditioning intensity (myeloablative vs. non-myeloablative) in a base model, to which we added the pre-transplantation ST2 level (linear) and assessed its incremental prognostic value [Steyerberg et al., Epidemiology, 2019]. The internal validity of the full model was estimated by bootstrapping [Steyerberg et al., J Clin Epidemiol, 2001]. Results: The median (Q1, Q3) pre-transplantation plasma ST2 level was 20.4 (15.2, 27.2) ng/mL. NRM at 1-year was 9% (N = 33). The main causes of NRM were organ failure (39%), infection (23%) and acute graft-versus-host disease (21%). Relapse risk at 1-year was 18%. The patients who constituted the 33 cases of 1-year NRM had a 2.7 ng/mL higher median pre-transplantation ST2 level than the remaining 341 patients (95% bootstrap confidence interval [CI] of the difference: -1.9, 6.2 ng/mL, Figure Panel A). In the full logistic regression model-including age, HCT-CI, conditioning intensity and ST2-ST2 was associated with 1-year NRM with an odds ratio of 1.32 (CI: 1.05, 1.65) per 10 ng/mL increase. Adding ST2 to the base model increased the model likelihood ratio χ 2 from 12.1 to 17.3 (p = 0.02), i.e. ST2 added a fraction of 30% (12.1/17.3) of new predictive information to age, HCT-CI and conditioning intensity. However, the ability of the full model to discriminate cases of NRM at 1-year remained poor with minimal improvement after adding ST2 (AUC up to 0.675 from 0.674 in the base model). The bootstrap-corrected AUC (the expected AUC of the full model used in a new population) was 0.63. Moreover, bootstrap-corrected estimates of predicted vs. observed risk revealed slight model miscalibration: lower predicted risks were generally underestimated, while higher predicted risks were overestimated (Figure Panel B). Conclusion: Pre-transplantation plasma levels of ST2 was a prognostic biomarker of 1-year NRM after allo-HCT, adding new predictive information to age, HCT-CI and conditioning intensity. However, internal validation of the full ST2-based prediction model revealed poor overall performance, precluding further validation and use of the model in clinical practice. When identifying prognostic biomarkers, investigation of overall predictive performance (in addition to already known prognostic factors) is needed before clinical usefulness can be evaluated. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
15. Donor Lymphocyte Infusion Is a Feasible Way to Improve Survival in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Who Relapse after Allogeneic Stem Cell Transplantation
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Lisbeth Pernille Andersen, Anne Fischer-Nielsen, Brian Kornblit, Joanne Reekie, Søren Lykke Petersen, Niels Smedegaard Andersen, Ida Schjødt, Henrik Sengeloev, Lone Smidstrup Friis, Lia Minculescu, and Eva Kannik Hastrup
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Oncology ,medicine.medical_specialty ,business.industry ,Myelodysplastic syndromes ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Donor lymphocyte infusion ,Transplantation ,Internal medicine ,medicine ,In patient ,Stem cell ,business - Abstract
Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) yet the major cause of death remains relapse after transplantation which occurs in 30-70% of patients for whom the prognosis is dismal. Since the 1990's donor lymphocyte infusion (DLI) has been proven able to induce remission after allo-HSCT and the use of therapeutic DLI at relapse has widely increased. The immunological mechanism in DLI is primarily T-cell-mediated graft-versus-leukemia (GVL) effect driven by genetic differences between donor and recipient in minor and major histocompatibility antigens. DLI treatment at relapse can additionally reverse T-cell exhaustion and increase T-cell receptor diversity, both of which are GVL-enhancing mechanisms. Risks and complications with DLI-treatment are primarily graft-versus-host disease (GVHD). Though dose escalation schedules have been suggested to increase the GVL-effect while minimizing the risk of GVHD, uniform therapeutic algorithms are still lacking, treatment is often individually scheduled, and outcome results are often disappointing with reported 2-year overall survival rates at 14-29% in AML relapse patients (Greiner J, Götz M, Bunjes D, Hofmann S, Wais V. Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients. J Clin Med. 2019;9(1):39). During the last decade, treatment with the hypomethylating agent azacitidin (Aza) has become another potential treatment in patients with myeloid malignancies. Immunological mechanisms of GVL in Aza-treatment for relapse include epigenetically reactivation of pro-apoptotic pathways and demasking of tumor-antigens while increased expression of regulatory T-cells protects from GVHD. In recent years DLI and Aza have been used for synergistical effect post-HSCT relapse both in patients who are un-fit to receive high-dose cytoreductive therapy as well as consolidation after reinduction. The aim of this analysis is to report results of retrospective single center-study of patients treated with DLI +/- Aza over a period of twenty years. Methods: Between 2001 and 2020 50 adult patients with relapse after allo-HSCT for AML(n=38) or MDS (n=12) were treated with DLI at the Department of Hematology, Transplant Unit, at Rigshospitalet, Copenhagen University Hospital, table 1. Only patients free from active GVHD were selected as DLI-candidates. Median follow-up time was 57 (1-170) months. Reinduction with high-dose chemotherapy was administered in 35 (70%) of patients prior to DLI and 34 (68%) patients were in complete morphological remission (CR) before DLI. DLI-products were unmanipulated and obtained from leukapheresis of unstimulated peripheral blood in matched related or unrelated donors of the original stem cell graft. Patients received a median of 3 (1-5) doses of DLI with median total doses of 6,1x10 7 (5x10 6- 4,65x10 8) CD3 postive T-cells per kg. Aza was used together with DLI from 2012 and administrered in 28 (56%) patients with a median of 6 (2-20) cycles. Reported outcomes are overall survial (OS) and relapse-free survival (RFS) in patients in CR prior to DLI. Results: At end of follow-up 20 patients were alive, 11 of these in CR and 2 in partial remission. In 7 patients, DLI was discontinued due to the development of GVHD after 1-2 doses, 6/7 of these patients had unrelated donors. Overall, 2 (4%) patients died from GVHD after DLI. Seven patients received a second HSCT after DLI treatment and were censored at this date in survival analyses. Figure 1a+b shows OS in all patients (n=50) and RFS in patients in CR prior to DLI (n=34). 2-year OS was approximately 59% and 5-year OS was 20%. 2-year RFS was approximately 32% and 5-year RFS was 8%. None of the analyzed baseline factors showed significant associations to the probability of OS, table 2, or RFS (data not shown). Reinduktion before first DLI and increasing doses of transplanted CD3 T cell per kg showed trends towards superior survival probability but failed to reach significant levels, possibly due to the limited patient number. Conclusion: Treatment vith DLI +/- Aza is effective and safe as relapse-treatment after allo-HSCT in myeloid diseases. In selected patients, a short-term (2-year) overall survival of 59% is achieved, and 20% of the patients remain long term survivors. Figure 1 Figure 1. Disclosures Fischer-Nielsen: A.F.N. is employee and shareholder of StemMedical A/S, a biotech company working with cell-enriched fat grafting.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company.
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- 2021
16. Does a Change in IPSS-R between Diagnosis and Transplant Have an Impact on Transplant Outcome in Patients with MDS? a Retrospective Analysis from the EBMT Chronic Malignancies Working Party
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Urs Schanz, Francesco Onida, Marie Robin, Didier Blaise, Ibrahim Yakoub-Agha, Martin Bornhäuser, Patrice Chevallier, Nicolaus Kröger, Jennifer Byrne, Jan J. Cornelissen, John A. Snowden, Dirk-Jan Eikema, Patrick Hayden, Jakob Passweg, Christof Scheid, Linda Koster, Henrik Sengeloev, Denis Guyotat, Jean-Henri Bourhis, Riitta Niittyvuopio, Amit R. Patel, Liesbeth C. de Wreede, Jürgen Finke, Tobias Gedde-Dahl, and Johan Maertens
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medicine.medical_specialty ,business.industry ,Internal medicine ,Immunology ,medicine ,Retrospective analysis ,In patient ,Cell Biology ,Hematology ,urologic and male genital diseases ,business ,Biochemistry ,Outcome (game theory) - Abstract
IPSS-R is a well established prognostic factor for transplant outcome in patients with MDS, irrespective whether it is assessed at diagnosis or at transplant. However it is unclear how a change in IPSS-R, e.g. by reducing bone marrow blasts through therapy, would potentially affect transplant results. In particular the decision to treat patients before transplant or perform an upfront allogeneic transplantation can so far not be based on evidence. We did a registry search based in the MDS quality initiative conducted by EBMT to identify transplanted patients with MDS and sufficient data to calculate IPSS-R at diagnosis and before transplant. The search was limited to patients reveiving a first allogeneic stem cell transplantation in the period 2005 -2018. 1482 patients were identified. Median age at alloHCT was 59 (interquartile range 51-64) years, 60% were male. Donors were related in 36%, graft source was PBSC in 85% of cases. Conditioning was standard dose in 33% and reduced intensity in 67%. IPSS-R both at diagnosis and at transplant had a significant impact on OS and RFS after alloHCT. To investigate the effect of a change in IPSS-R between diagnosis and transplant we constructed 3 subgroups: stable IPSS-R, improved IPSS-R, worsened IPSS-R. A change in IPSS-R was noted in 77.5% of patients with prior chemotherapy, 72% with prior HMA and 59.8% of untreated patients. Univariate analysis showed no significant difference in OS or RFS in patients with stable IPSS-R compared to improved or worsened IPSS-R. In patients treated with chemotherapy before transplant OS and RFS was significantly worse with worsened IPSS-R, while this effect was not found in patient treated with hypomethylating agents (HMA) or untreated patients. The same analysis was performed regarding the difference in bone marrow blasts and the cytogenetics score: OS and RFS after transplant were significantly worse with increased blasts (p=0.04 and p=0.001) and a worsened cytogenetic score before transplant (both p In this retrospective analysis from a large cohort of patients with MDS we found that worsening of IPSS-R, blast count or cytogenetic score had a negative prognostic impact in chemotherapy-treated patients, while only worsened blast count and cytogenetics were significant negative factors in HMA-treated or untreated patients. Conversely we did not find a positive effect of improved IPSS-R, decreased blasts or improved cytogenetics in any of the subgroups of treated or untreated patients. Thus for MDS patients receiving an allogeneic transplantation our results provide no clear signal that prior therapy is able to improve transplant outcome. Disclosures Scheid: Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria; Takeda: Honoraria, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria. Chevallier:Incyte Corporation: Honoraria. Yakoub-Agha:Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria.
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- 2020
17. Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell–Replete Allogeneic Hematopoietic Stem Cell Transplantation
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Hanne Vibeke Marquart, Lia Minculescu, Lars P. Ryder, Henrik Sengeloev, Ida Schiødt, Lone Smidstrup Friis, Soeren Lykke Petersen, and Niels Smedegaard Andersen
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Adult ,Male ,0301 basic medicine ,Adolescent ,medicine.medical_treatment ,Cell ,Hematopoietic stem cell transplantation ,Infections ,Natural killer cell ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Cumulative incidence ,Lymphocyte Count ,Aged ,Transplantation ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Allografts ,Prognosis ,Killer Cells, Natural ,Survival Rate ,Leukemia, Myeloid, Acute ,030104 developmental biology ,medicine.anatomical_structure ,Myelodysplastic Syndromes ,Immunology ,business ,030215 immunology - Abstract
Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate the clinical impact of early NK cell recovery in T cell–replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013. In multivariate analysis NK cell numbers on day 30 (NK30) > 150 cells/µL were independently associated with superior overall survival (hazard ratio, .79; 95% confidence interval, .66 to .95; P = .01). Cumulative incidence analyses showed that patients with NK30 > 150 cells/µL had significantly less transplant-related mortality (TRM), P = .01. Patients with NK30 > 150 cells/µL experienced significantly lower numbers of life-threatening bacterial infections as well as viral infections, including cytomegalovirus. No association was observed in relation to relapse. These results suggest an independent protective effect of high early NK cell reconstitution on TRM that translates into improved overall survival after T cell–replete HSCT.
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- 2016
18. Outcome of Allogeneic Haematopoietic Stem Cell Transplantation in Myeloproliferative Neoplasms-Unclassifiable: A Retrospective Study By the Chronic Malignancies Working Party of EBMT
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Dragana Milojkovic, Dietrich W. Beelen, Marie Robin, Victoria Potter, Fabio Ciceri, Sonja Martin, Donald Bunjes, Donal P. McLornan, Yves Beguin, Linda Koster, Ibrahim Yakoub-Agha, Simona Iacobelli, Yves Chalandon, Ernst Holler, Nicolaus Kröger, Jakob Passweg, Bruno Lioure, Aleksandar Radujkovic, Tomasz Czerw, Patrick Hayden, Anne Lippinkhof-Kozijn, Martin Bornhäuser, Vittoria Malpassuti, Gerald Wulf, Jan-Erik Johansson, Henrik Sengeloev, and Juan Carlos Hernandez Boluda
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Medizin ,Retrospective cohort study ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Fludarabine ,Transplantation ,Haematopoiesis ,Graft-versus-host disease ,Internal medicine ,Medicine ,Stem cell ,business ,Busulfan ,medicine.drug - Abstract
Introduction Myeloproliferative Neoplasm (MPN) unclassifiable (MPN-U), is a heterogeneous disease that presents with an MPN-type clinical/ histological phenotype yet fails to meet diagnostic criteria for other MPN entities. Incidence is Methods This registry-based analysis was approved by the Chronic Malignancies Working Party of the EBMT. Patient selection was performed by identifying adult patients who underwent first allo-HCT for MPN-U between 2000-2015, using either Reduced Intensity Conditioning (RIC) or Myeloablative conditioning (MAC) as defined by standard EBMT criteria. Further data collection requests (MED-C) forms were sent to centres to improve data completeness. Statistical analyses were performed with SPSS 22 (SPSS Inc./IBM, Armonk, NY) and R. Overall Survival (OS) was calculated from the date of transplant until death or last observation alive. Cumulative incidence functions were used to estimate Non-Relapse Mortality (NRM) and Relapse Incidence (RI) within a competing risk setting. Results A total of 70 patients, 48 (69%) male and 22 (31%) female, with a confirmed diagnosis of MPN-U were analysed. Median age was 57 years (range (r), 22-70 years). Of these patients, 37 (53%) underwent allo-HCT in the period 2001-2010 and 33 (47%) between 2011-2015. MAC regimens were utilised in 31 (44%) patients while 39 (56%) received RIC. Patients were most frequently transplanted within the first two years from diagnosis, with a median time to allo-HCT of 13 months (r, 3-244 months). Diagnostic karyotype was normal in 36 (51%) and abnormal in 23 (33%) patients, with data missing for 11 (16%) patients. A total of 45 (64%) patients had received prior treatment, 23 (33%) patients were untreated and data was incomplete in 2 (3%) patients. Regarding donor type, 27 (39%) patients had a Matched Sibling Donor (MSD) and 43 (61%) an Unrelated Donor (URD). Most frequent conditioning regimens were TBI-based in the MAC cohort and Fludarabine-Busulphan in the RIC cohort. A trend towards higher rates of delayed/failed engraftment was noted in the RIC compared to MAC cohort (p=0.09). Where successful, median time to neutrophil engraftment in both cohorts was similar (18 days for MAC and 17 for RIC) and both platforms demonstrated similar platelet engraftment times (17.5 days). Incidence of grade II-IV aGVHD at 3 months was higher in the MAC (37%) compared to RIC cohort (16%; p=0.05) and the 12-month cumulative incidence of cGVHD for MAC was 52% (95%CI: 32.4, 71.6) and for RIC 32.1% (95%CI: 14.8, 49.4; p=0.117)). Median follow-up was 87 months (minimum and maximum of censored cases: 31 and 196 months). The median OS estimates at 1, 3 and 5-year were 77%, 55% and 42% (MAC) and 59%, 44% and 41% (RIC), respectively (p=0.33). No significant difference existed in OS rates between those who had pre-transplant therapy versus not. Relapse remained significant: cumulative incidences of relapse at 1,3 and 5-years were 10%, 23% and 27% (MAC) and 28%, 36% and 36% (RIC), respectively (p=0.28). NRM probabilities at 1, 3 and 5-years post allo-HCT were also considerable: 19%, 29%, and 34% (MAC) and 28%, 28% and 28% (RIC), respectively (p=0.84). Main causes of NRM were infection and GVHD. Univariate analysis associated use of an URD with a significantly worse OS and NRM compared with MSD. Moreover, the presence of abnormal karyotype at time of allo-HCT was associated with a trend towards a higher risk of relapse (p=0.06). Conclusions This study highlights the potentially curative role of allo-HCT in MPN-U and provides clinicians with robust engraftment, GVHD and outcome data. Both engraftment and OS rates appear acceptable yet NRM and CIR rates in both settings remain high and need to be addressed. The impact of abnormal karyotype at the time of allo-HCT and a trend towards higher risks of relapse requires further elucidation. Disclosures McLornan: Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria, Speakers Bureau. Robin:Novartis Neovii: Research Funding. Chalandon:Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte Biosciences: Consultancy, Honoraria. Beelen:Medac GmbH Wedel Germany: Consultancy, Honoraria. Kröger:Sanofi-Aventis: Honoraria; Riemser: Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Medac: Honoraria; JAZZ: Honoraria; DKMS: Research Funding; Celgene: Honoraria, Research Funding. Milojkovic:Novartis: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau. Hernandez Boluda:Incyte: Other: Travel expenses paid.
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- 2019
19. Outcomes Following Second Allogenic Haematopoietic Cell Transplantation in Patients with Myelofibrosis: A Retrospective Study on Behalf of the Chronic Malignancies Working Party of EBMT
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Martin Bornhäuser, Liesbeth C. de Wreede, Fabio Ciceri, Mitja Nabergoj, Nicolaus Kröger, Uwe Platzbecker, Donal P. McLornan, Henrik Sengeloev, Tomasz Czerw, Linda Koster, Yves Chalandon, Peter Dreger, Emanuele Angelucci, Marie Robin, Stephen D. Robinson, Marco Ladetto, Matthias Stelljes, Ibrahim Yakoub-Agha, Alessandro Rambaldi, Xavier Poiré, Juan Carlos Hernandez Boluda, Jakob Passweg, Jiri Mayer, Junfeng Wang, and Patrick Hayden
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0301 basic medicine ,medicine.medical_specialty ,Graft failure ,Graft rejection ,Karnofsky Performance Status ,business.industry ,Immunology ,Haematopoietic cell transplantation ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Curative treatment ,Family medicine ,Honorarium ,Medicine ,In patient ,business ,health care economics and organizations ,030215 immunology - Abstract
Introduction: The only curative treatment for myelofibrosis (MF) remains allogenic haematopoietic cell transplantation (allo-HCT) although the risks of non-relapse mortality (NRM), relapse and graft rejection need to be taken into consideration. Therapeutic approaches following relapse after allo-HCT include symptom-directed management, chemotherapy, JAK2 inhibitors, adoptive immunotherapeutic approaches with donor lymphocyte infusion (DLI) and, in a minority, a second allo-HCT. Frequently, due to the advanced age of the recipient, early relapses, and numerous complications, 2nd allo-HCT can only be considered in a limited number of patients. Few studies evaluating the role of 2nd allo-HCT in MF following 1st relapse or primary/secondary graft rejection have been published to date. Methods and results: Patient selection was performed by identifying adult patients who underwent 2nd allo-HCT for MF between 2010-2017: 216 patients were analyzed; 64% were male, 78% had primary MF (PMF) and 22% secondary MF (sMF). Median age at the time of 2nd allo-HCT was 57 years, and median time from 1st allo-HCT was 8 months. Of this cohort, 56% of patients received a 2nd allo-HCT for relapse, 31% for graft failure and the reason was missing in 13%. A greater proportion was transplanted within 1 year from 1st allo-HCT (61 %) whilst 39% had 2nd allo-HCT > 1 year. A reduced Karnofsky performance status (KPS12 months, p=0.02). The 2-year relapse-free-survival (RFS) for the entire cohort was 44%. Only time elapsed from the 1st allo-HCT to 2nd was significantly associated with 2-year RFS (41% for ≤12 months, 49% for >12 months, p=0.05). Of note, the 2-year OS and RFS were comparable following use of the same or a different donor. The 2-year cumulative incidence of relapse and NRM were 22 and 34%, respectively. The time interval from 1st to 2nd allo-HCT appeared to be highly significant for NRM with patients transplanted ≤12 months having a higher 2-year NRM compared to those transplanted >12 months (40 vs 24%, respectively, p=0.008). A trend for higher NRM was the reason for 2nd allo-HCT: patients transplanted for graft rejection had a 2-year NRM of 45% compared to 31% for those with relapse (p=0.06). Conclusions: This analysis supports the utilization of a 2nd allo-HCT for patients with MF who have presented with graft failure or relapse following a 1st allo-HCT. In univariate analysis, overall outcome appears worse in patients being transplanted after graft failure as well as for those transplanted within 1 year after 1st allo-HCT, due to increased NRM. Of note, the use of either the original or a different donor are associated with similar outcomes. Further work is required to elucidate other risk factors, GVHD rates and to define the optimal conditioning regimen in this setting. Table. Disclosures Robin: Novartis Neovii: Research Funding. Kröger:Sanofi-Aventis: Honoraria; Riemser: Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Medac: Honoraria; JAZZ: Honoraria; DKMS: Research Funding; Celgene: Honoraria, Research Funding. Angelucci:Celgene: Honoraria, Other: Participation in DMC; BlueBirdBio: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; Roche: Other: Local advisory board; Vertex Pharmaceuticals Incorp., and CRISPR Therapeutics: Other: Participation in DMC; Novatis: Honoraria, Other: Chair Steering Committee TELESTO protocol. Dreger:AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; Neovii, Riemser: Research Funding. Platzbecker:Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Rambaldi:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mayer:AOP Orphan Pharmaceuticals AG: Research Funding. Ladetto:ADC Therapeutics: Honoraria; Pfizer: Honoraria, Speakers Bureau; Celgene: Honoraria; J&J: Honoraria; Roche: Honoraria; AbbVie: Honoraria; Acerta: Honoraria, Speakers Bureau. Hernandez Boluda:Incyte: Other: Travel expenses paid. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria. Chalandon:Incyte Biosciences: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.
- Published
- 2019
20. Cord Blood Unit Dominance Analysis and Effect of the Winning Unit on Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: A Retrospective Study on Behalf of Eurocord, the Cord Blood Committee of Cellular Therapy, Immunobiology Working Party, and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation
- Author
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Charles Craddock, Nigel H. Russell, Henrik Sengeloev, Thierry Lamy, Pierre-Simon Rohrlich, Maud D'Aveni, Vanderson Rocha, Mauricette Michallet, Arnon Nagler, Karina Tozatto-Maio, Eric Deconinck, Eliane Gluckman, Edouard Forcade, Annalisa Ruggeri, Chantal Kenzey, Hiromi Hayashi, Jan J. Cornelissen, Regis Peffault de la Tour, Federica Giannotti, Fernanda Volt, Annalisa Paviglianiti, Didier Blaise, Myriam Labopin, Eefke Petersen, Dimitrios Karakasis, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Centre International des greffes [CHU Saint-Antoine] (EBMT), 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 d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], France Monacord, Centre Scientifique de Monaco (CSM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital l'Archet, 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), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], University Medical Center [Utrecht], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Rigshospitalet [Copenhagen], Copenhagen University Hospital, CHU Pontchaillou [Rennes], Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre for Clinical Haematology [Birmingham, UK], Queen Elizabeth Hospital [Birmingham, UK], Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, and Hematology
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Adult ,Male ,medicine.medical_specialty ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Retrospective Studies ,Transplantation ,Acute leukemia ,Transplantation Chimera ,Neutrophil Engraftment ,Leukemia ,Umbilical Cord Blood Transplantation ,business.industry ,Hazard ratio ,Retrospective cohort study ,Hematology ,HLA Mismatch ,Survival Analysis ,HLA ,030220 oncology & carcinogenesis ,Cord blood ,Double-Unit Umbilical Cord Blood Transplantation ,Histocompatibility ,Acute Disease ,Double cord blood transplantation ,Winning cord blood unit ,Female ,Cord Blood Stem Cell Transplantation ,business ,SOBREVIDA ,030215 immunology ,Unit dominance - Abstract
International audience; Usually, after double umbilical cord blood transplantation (DUCBT), only 1 of the transplanted units persists in the long term. The characteristics of the winning cord blood unit (W-CBU) that determine unit dominance and how they influence the outcomes of DUCBT remain unclear. We retrospectively analyzed 347 patients with acute leukemia transplanted with a DUCBT (694 CBU) from 2005 to 2013 who had documented neutrophil engraftment and a W-CBU identified by chimerism analysis, to identify unit characteristics impacting on dominance. Median age at DUCBT was 40 years and median follow-up was 35 months. Among W-CBUs, 41% were ≥5/6 HLA matched to the recipient and 59% were ≤4/6. Multivariate analysis indicated that ≤4/6 HLA-matched W-CBUs led to lower leukemia-free survival (44% versus 56%; hazard ratio [HR], 1.5; P = .032) and overall survival (49% versus 62%; HR, 1.5; P = .028), increased nonrelapse mortality (26% versus 18%; HR, 1.9; P = .027), and acute graft-versus-host disease (46% versus 35%; HR, 1.7; P = .013). We were unable to predict unit dominance, but we demonstrated that outcomes were strongly influenced by the degree of HLA mismatch between W-CBU and recipient. Therefore, selection of both units with the lower number of HLA mismatches with the recipient is indicated.
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- 2017
21. Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation
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Laurent Pascal, Eliane Gluckman, Eurocord, Chantal Kenzey, Marrow Transplantation, Patrice Chevallier, Werner Linkesch, Ernst Holler, Eefke Petersen, Luciana Tucunduva, Hermann Einsele, Reza Tabrizi, Patrice Ceballos, Antonio Pagliuca, Annalisa Ruggeri, Didier Blaise, Vanderson Rocha, Natacha Maillard, Henrik Sengeloev, Ibrahim Yakoub-Agha, Jan J. Cornelissen, and Hematology
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Cyclophosphamide ,Immunology ,Graft vs Host Disease ,Kaplan-Meier Estimate ,Biochemistry ,Gastroenterology ,Young Adult ,Internal medicine ,Humans ,Medicine ,Myeloproliferative neoplasm ,Aged ,Antilymphocyte Serum ,Proportional Hazards Models ,business.industry ,Umbilical Cord Blood Transplantation ,Incidence (epidemiology) ,Hazard ratio ,Cell Biology ,Hematology ,Middle Aged ,Total body irradiation ,Allografts ,medicine.disease ,Lymphoproliferative Disorders ,Surgery ,Fludarabine ,Regimen ,Myelodysplastic Syndromes ,Female ,Cord Blood Stem Cell Transplantation ,business ,Vidarabine ,Whole-Body Irradiation ,medicine.drug - Abstract
We analyzed 661 adult patients who underwent single-unit (n = 226) or double-unit (n = 435) unrelated cord blood transplantation (UCBT) following a reduced-intensity conditioning (RIC) consisting of low-dose total body irradiation (TBI), cyclophosphamide, and fludarabine (Cy/Flu/TBI200). Eighty-two patients received rabbit antithymocyte globulin (ATG) as part of the conditioning regimen (ATG group), whereas 579 did not (non-ATG group). Median age at UCBT was 54 years, and diagnoses were acute leukemias (51%), myelodysplastic syndrome/myeloproliferative neoplasm (19%), and lymphoproliferative diseases (30%). Forty-four percent of patients were transplanted with advanced disease. All patients received ≥4 antigens HLA-matched UCBT. Median number of collected total nucleated cells was 4.4 × 10(7)/kg. In the ATG group, on 64 evaluable patients, ATG was discontinued 1 (n = 27), 2 (n = 20), or > 2 days before the graft infusion (n = 17). In multivariate analyses, the use of ATG was associated with decreased incidence of acute graft-versus-host disease (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.17-0.55; P < .0001), higher incidence of nonrelapse mortality (HR, 1.68; 95% CI, 1.16-2.43; P = .0009), and decreased overall survival (HR, 1.69; 95% CI, 1.19-2.415; P = .003). Collectively, our results suggest that the use of ATG could be detrimental, especially if given too close to graft infusion in adults undergoing UCBT following Cy/Flu/TBI200 regimen.
- Published
- 2015
22. Impact of postremission consolidation chemotherapy on outcome after reduced-intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission: A report from the Acute Leukemia Working Party of
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Lars Vindeløv, Patrice Chevallier, Henrik Sengeloev, Gérard Socié, Karin Bilger, Arnon Nagler, Mohamad Mohty, Hakan Goker, Donald Bunjes, Renate Arnold, Moshe Yeshurun, Myriam Labopin, Nathalie Fegueux, Johan Maertens, Jan J. Cornelissen, Charles Craddock, J. Kuball, Harry C. Schouten, and Didier Blaise
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Adult ,Male ,Oncology ,Antimetabolites, Antineoplastic ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Graft vs Host Disease ,Disease-Free Survival ,Young Adult ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Aged ,Retrospective Studies ,Acute leukemia ,business.industry ,Hazard ratio ,Cytarabine ,Cancer ,Myeloid leukemia ,Consolidation Chemotherapy ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,Transplantation ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Female ,Neoplasm Recurrence, Local ,business ,Immunosuppressive Agents ,Stem Cell Transplantation ,medicine.drug - Abstract
BACKGROUND The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). METHODS Of the 789 consecutive patients with AML in CR1 who underwent RIC alloSCT from a human leukocyte antigen-matched sibling or matched unrelated donor peripheral stem cell grafts between 2001 and 2010, 591 patients received at least 1 cycle of consolidation chemotherapy and 198 patients did not receive any consolidation chemotherapy before alloSCT. To minimize inherent survival bias in favor of patients who underwent transplant long after achieving CR1, the study focused on 373 patients who underwent transplant within the median time frame between achievement of CR1 and alloSCT (3 months for patients who underwent alloSCT from matched siblings and 4 months for patients who underwent alloSCT from matched unrelated donors). In this subgroup, 151 patients did not receive any consolidation chemotherapy and 222 patients received ≥ 1 consolidation chemotherapy cycle. RESULTS With a median follow-up of 36 months (range, 2 months-135 months), the 3-year cumulative recurrence incidence (RI) was not significantly different between the groups (36% ± 4% for the group treated without consolidation chemotherapy vs 38% ± 3% for patients who received consolidation chemotherapy; P = .89). In addition, leukemia-free survival was similar between the groups (45% ± 4% and 47% ± 3%, respectively; P = .41). Dose intensity of cytarabine given during consolidation chemotherapy appeared to have no influence on RI. On multivariate analysis, pretransplant consolidation (≥ 1 cycle vs 0 cycles) was found to have no significant impact on RI (hazards ratio, 1.29; 95% confidence interval, 0.84-1.97 [P = .24]) or leukemia-free survival (hazards ratio, 1.00; 95% confidence interval, 0.71-1.42 [P = .99]). CONCLUSIONS The data from the current study suggest no apparent advantage for postremission consolidation chemotherapy before RIC alloSCT, provided a donor is readily available. Cancer 2014;120:855–863. © 2013 American Cancer Society.
- Published
- 2013
23. Improved Relapse-Free Survival and Overall Survival in Patients with High Immune Reconstitution of Gamma Delta T Cells 2 Months after Allogeneic Hematopoietic Stem Cell Transplantation
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Brian Kornblit, Lars P. Ryder, Niels Smedegaard Andersen, Henrik Sengeloev, Lone Smidstrup Friis, Anne Fischer-Nielsen, Eva Kannik Hastrup, Ida Schjødt, Søren Lykke Petersen, Hanne Vibeke Marquart, and Lia Minculescu
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biology ,business.industry ,medicine.medical_treatment ,CD3 ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,NKG2D ,Biochemistry ,Transplantation ,Leukemia ,Graft-versus-host disease ,Immune system ,biology.protein ,Medicine ,business ,CD8 - Abstract
Introduction: The role of T cell receptor (TCR) γδ cells in allogeneic hematopoietic stem cell transplantation (HSCT) is becoming of increasing interest1,2. In contrast to conventional alloreactive TCR αβ cells, TCR γδ cells are believed to have anti-tumor effects without causing graft-versus-host disease (GVHD). We conducted a single-center, prospective study to assess the impact of early TCR γδ cell immune reconstitution on overall survival, relapse and acute GVHD after HSCT. Methods: From October 2015 to March 2017, 108 consecutive patients transplanted for malignant diseases at the Bone Marrow Transplant Unit, Department of Hematology, Copenhagen University Hospital, Rigshospitalet, were included in the study, table 1. Fresh blood samples days 28, 56, 91, 180 and 360 after transplantation were analyzed for absolute concentrations of CD3-, CD4- and CD8 positive T cells together with a multi-color flow cytometry panel with staining for TCRαβ, TCRγδ, Vδ1, Vδ2, CD3, CD4, CD8, HLA-DR, CD196, CD45RO, CD45RA, CD16, CD56, CD314 (NKG2D) and CD337 (NKp30) for immune phenotyping. Results: After a median of 673 (386-913) days, 28 (26%) patients had died from relapse (n=14) and from transplant-related-mortality(n=14), respectively. A total of 24 (22%) patients experienced relapse during the observation time with median time to relapse of 177 (56-778) days. Acute GVHD grade 2-4 was diagnosed in 38 (35%) of patients. Patients were divided into two groups by dichotomization at the median value of TCR γδ cell concentrations for Kaplan-Meier analyses of overall survival (OS), relapse-free survival (RFS) and cumulative incidence analyses (Gray's test for competing risks) of relapse and acute GVHD. Patients with high concentrations of TCR γδ cells 56 days after transplantation had significantly higher OS and RFS compared with patients with low concentrations, p Conclusion: The results of this prospective study suggest a protective effect of early robust TCR γδ cell immune reconstitution on relapse and acute GVHD resulting in increased OS after HSCT, and support further research in adoptive TCR γδ cell therapy in transplant patients. Handgretinger, R. & Schilbach, K. The potential role of gd T cells after allogeneic HCT for leukemia. Blood131, 1063-1072 (2018). Scheper, W., Grunder, C., Straetemans, T., Sebestyen, Z. & Kuball, J. Hunting for clinical translation with innate-like immune cells and their receptors. Leukemia28, 1181-1190 (2014). Disclosures No relevant conflicts of interest to declare.
- Published
- 2018
24. Outcomes after Unrelated Cord Blood Transplantation (UCBT) in Patients with Chronic Myeloid Leukemia (CML): A Retrospective Study from the Cmwp-EBMT
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Ibrahim Yakoub-Agha, Tony Marchand, Jorge Sierra, Victoria Potter, Anna Paola Iori, Francesca Bonifazi, Emanuele Angelucci, Jaime Sanz, Jan J. Cornelissen, Tobias Gedde-Dahl, Simona Lapusan, Giulia Sbianchi, Hugues de Lavallade, Didier Blaise, Yves Chalandon, Hélène Labussière-Wallet, Henrik Sengeloev, Annalisa Ruggeri, Martin Carre, Gérard Socié, Linda Koster, Eefke Petersen, Cécile Pochon, Per Ljungman, Isabelle Pietri, and Nigel H Russel
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Umbilical Cord Blood Transplantation ,business.industry ,medicine.medical_treatment ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,medicine.disease ,Biochemistry ,Transplantation ,Leukemia ,Graft-versus-host disease ,medicine ,Stem cell ,business - Abstract
The introduction of tyrosine kinase inhibitors (TKIs) to treat chronic myelogenous leukemia (CML), has largely replaced curative strategies based on allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT continue to be recommended for patients progressing to a more advanced phase of the disease and those in first chronic phase (CP1) failing second and third generation TKIs. Although the role of allogeneic HSCT using matched related or unrelated donor remains well established in the post-TKI era, controversies exist in transplant using alternative donors, and data in this setting is scarce. Umbilical cord blood (UCB) can be used as an alternative stem cell source for patients in whom allogeneic HSCT is indicated, but lack an appropriate human leucocyte antigen (HLA)-matched adult donor. The advantages of UCBT include rapid availability, absence of donor risk, and the relatively lower risk of GVHD with preserved graft versus leukemia effect. Because of the lack of large studies on the outcome of UCBT for CML patients in the TKI era, we performed a retrospective analysis to identify risk factors for outcomes after unrelated cord blood transplants in adults with CML. Through the EBMT database, 150 CML patients were identified as UCBT recipients. Median year of UCBT was 2008 (range, 2000 to 2015) with a median follow up of 62.2 months (range, 3 to 203.1 months). Median age at the time of transplant was 40.4 years (range, 18.8 to 66.5) with a male to female ratio of 92/58. The median time from CML diagnosis to UCBT was 29.9 months (range, 3.4 to 273.6) with first (Q1) and third (Q3) quartile at 12.4 and 57.3 months respectively. Eleven patients received an UCBT as a second allogeneic HSCT. Conditioning regimen was of reduced intensity (RIC) in 44 patients while 92 received a myeloablative conditioning (MAC), and 61 out of 128 evaluable patients received T-cell depletion. Disease status at the time of transplant was first chronic phase (CP1, n=45), second or third chronic phase (CP2 and CP3, n=48) or advanced phase (accelerated phase or blastic phase, AP/BP, n=55). Overall survival (OS) at 12, 24 and 36 months were 52.1% (95% CI 44.0 to 60.1%), 44.5% (95% CI 36.3 to 52.6 %) and 41.2% (95% CI 33.0% to 49.4%) respectively. Median time to neutrophil and platelet engraftment were 23 and 47 days respectively in 119 patients who engrafted, while 24 and 7 patients experienced primary (16%) or secondary (4.6%) graft failure respectively. At 24 months, the cumulative incidence of non-relapse mortality (NRM) and relapse were 38.9% (95% CI 31.0 to 46.9%) and 25.3% (95% CI 18.2% to 32.3%), while cumulative incidence of grade 2-4 acute GvHD was 34.3% (95% CI 26.1 to 42.5%) and 24 months cumulative incidence of chronic GvHD was 24.8% (95% CI 15.6 to 34.0%). OS and disease-free survival (DFS) were significantly reduced for patients in AP/BP at the time of transplant compared to patients in CP1 or CP2/CP3 (24 months OS, 27.1% vs 55.3% and 53.7%, p=0.0026; 24 months DFS, 21.5% vs 39.4% and 47.1% respectively, p=0.0059, Figure 1). Cumulative incidence of relapse was significantly increased in patients in AP/BP at the time of HSCT compared to patient in CP1 or CP2/3 (24 months relapse incidence of 37.6% vs 20.6% and 17.1% respectively, p=0.0178). There was no significant difference in OS and DFS in patients receiving RIC compared to MAC (24 months OS 47.1 and 48.1% respectively, p=0.8; 24 months DFS 33% vs 40.6%, p=0.36). Cumulative incidence of relapse at 24 months was 34.7% in RIC and 24.6% in MAC, although this was not statistically significant (p=0.14). In conclusion, UCBT is more effective in CML patients who are in first CP but also in those who are in second or third CP at the time of transplant. NRM remains high, possibly related to differences in practices of UCBT over time and between centers. Comparison with alternative graft source such as haploidentical HSCT is needed, although little data is available in this setting. Patients who are in advanced phase disease at the time of transplant have a dismal prognosis comparable to those who receive an allogeneic HSCT from HLA-matched adult donors, although pre and post-transplant intervention with 3rd generation TKI may help improve outcome of these patients. Finally the use of RIC regimen for UCBT is an alternative for patients who cannot tolerate a MAC regimen; further analysis will help identify patients who would benefit from this approach. Figure 1. Figure 1. Disclosures De Lavallade: Incyte: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Angelucci:Jazz Pharmaceuticals Italy: Other: Local ( national) advisory board; Vertex Pharmaceuticals Incorporated (MA) and CRISPR CAS9 Therapeutics AG (CH): Other: Chair DMC; Roche Italy: Other: Local (national) advisory board; Celgene: Honoraria, Other: Chair DMC; Novartis: Honoraria, Other: Chair Steering Comiittee TELESTO Protocol. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.
- Published
- 2018
25. In Selected Older Patients (Pts) Non-Myeloablative (NMA) Based Allogeneic Haematopoietic Cell Transplantation (alloHCT) Reach Acceptable Morbidity and Survival. a Danish Retrospective Single Center Study
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Niels Smedegaard Andersen, Ida Schioedt, Henrik Sengeloev, Søren Lykke Petersen, Brian Kornblit, and Lone Smidstrup Friis
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Transplantation ,Pediatrics ,medicine.medical_specialty ,business.industry ,Haematopoietic cell transplantation ,Non myeloablative ,Hematology ,Single Center ,language.human_language ,Danish ,Older patients ,language ,Medicine ,business - Published
- 2018
26. Innate Effector Cells in Stem Cell Grafts for Allogeneic Transplantation
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Anne Fischer-Nielsen, Lia Minculescu, Hanne Vibeke Marquart, Lars P. Ryder, Hans O. Madsen, Henrik Sengeloev, and Eva Haastrup
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Transplantation ,Allogeneic transplantation ,business.industry ,Effector ,Immunology ,Medicine ,Hematology ,Stem cell ,business - Published
- 2018
27. Impact of Donor Type in Patients with AML Receiving Allogeneic Hematopoietic Cell Transplantation after Low-Dose TBI Based Conditioning: A Study From the Alwp of the Ebmt and Eurocord
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Annalisa Ruggeri, Bipin N. Savani, Didier Blaise, Jan J. Cornelissen, Ellen Meijer, Dietger Niederwieser, Marco R. de Groot, Eliane Gluckman, Mohamad Mohty, Noel Milpied, Arnon Nagler, Harry C. Schouten, Myriam Labopin, Frédéric Baron, and Henrik Sengeloev
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Oncology ,Transplantation ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Internal medicine ,Low dose ,Medicine ,In patient ,Hematology ,business - Published
- 2018
28. Association of HMGB1 Polymorphisms with Outcome after Allogeneic Hematopoietic Cell Transplantation
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Søren Lykke Petersen, Brian Kornblit, Henrik Sengeloev, Hans O. Madsen, Lars Vindeløv, Lone Schejbel, Peter Garred, Klaus Müller, Tania N. Masmas, and Carsten Heilmann
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Male ,Heterozygote ,Linkage disequilibrium ,Transplantation Conditioning ,medicine.medical_treatment ,Statistics as Topic ,Immunology ,Graft vs Host Disease ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Linkage Disequilibrium ,Proinflammatory cytokine ,Cohort Studies ,Loss of heterozygosity ,Gene Frequency ,Recurrence ,medicine ,Humans ,Transplantation, Homologous ,Progression-free survival ,HMGB1 Protein ,Allele frequency ,Genetic Association Studies ,HMGB1 ,Transplantation ,Genetic polymorphism ,business.industry ,Homozygote ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Myeloablative Agonists ,Allogeneic hematopoietic cell transplantation ,medicine.disease ,Minor allele frequency ,Systemic inflammatory response syndrome ,Treatment Outcome ,Graft-versus-host disease ,Cytokine ,Hematologic Neoplasms ,Female ,High mobility group box 1 protein ,Bone Marrow Neoplasms ,business - Abstract
Abstract 2260 Poster Board II-237 Several studies have demonstrated that genetic variation in cytokine genes can modulate the immune reactions after allogeneic hematopoietic cell transplantation (HCT). High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a proinflammatory signal, important for the activation of antigen presenting cells (APC) and propagation of inflammation. HMGB1 is implicated in the pathophysiology of a variety of inflammatory diseases, and we have recently found the variation in the HMGB1gene to be associated with mortality in patients with systemic inflammatory response syndrome (SIRS). To assess the impact of the genetic variation in HMGB1 on outcome after allogeneic HCT, we genotyped 276 and 146 patient/donor pairs treated with allogeneic HCT for hematologic malignancies following myeloablative or non-myeloablative conditioning. Associations between genotypes and outcome were only observed in the cohort treated with myeloablative conditioning. Patient homozygosity or heterozygosity for the –1377delA minor allele was associated with increased risk of relapse (hazard ratio (HR) 2.11, P=0.02) and increased relapse related mortality (RRM) (P=0.03). The –1377delA minor allele has previously been associated with mortality in patients with SIRS, and although SIRS and allogeneic HCT are different entities the confirmative association of this polymorphic locus with mortality in 2 independent studies suggests that it is of pathophysiological importance. The three polymorphisms, 3814C>G, 1177G>C and 2351insT, tended to have the same effect on transplantation outcome, due to a moderate to strong linkage disequilibrium between loci. Of these three polymorphisms, patient homozygosity for the 3814C>G minor allele showed the strongest association with increased overall survival (HR 0.13, P=0.04), progression free survival (HR 0.30, P=0.05) and decreased probability of RRM (P=0.03). Patient carriage of the 2351insT minor allele reduced the risk of grade 2 to 4 acute graft versus host disease (GVHD) (HR 0.60, P=0.01), while donor carriage of the minor allele displayed a gene dosage effect, with a successive increase in risk of developing limited or extensive chronic GVHD per minor allele carried (HR 1.54, P=0.01). That patient HMGB1 genotypes were associated with outcomes dependent on primarily patient APCs, and that donor genotypes were associated with a, in part, donor APC dependent outcome, could suggest that the polymorphisms in HMGB1 influence the transcription of HMGB1 in APCs induced by the proinflammatory milieu after myeloablative conditioning, rather than the passively released from damaged cells, although these two mechanisms are not mutually exclusive. Our findings suggest that the inherited variation in HMGB1 is associated with outcome after allogeneic HCT following myeloablative conditioning. None of the polymorphisms were associated with treatment related mortality. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2010
29. Outcome of Third Salvage Autologous Stem Cell Transplantation in Multiple Myeloma
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Hervé Tilly, Arnold Ganser, Mariella Grasso, Denis Caillot, Pavel Zak, Xavier Leleu, Bernd Metzner, Stefan Schoenland, Linda Koster, Simona Iacobelli, Fabio Ciceri, Peter Dreger, David Pohlreich, Dominique Bron, Michael Potter, Jiri Mayer, Nicolaus Kröger, Laurent Garderet, Herman Einsele, Christian Peschel, Anja van Biezen, Jan-Erik Johansson, Henrik Sengeloev, Giuseppe Saglio, and Kerstin Schäfer-Eckart
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Melphalan ,Cancer Research ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Conditioning regimen ,Transplantation ,03 medical and health sciences ,First relapse ,0302 clinical medicine ,Autologous stem-cell transplantation ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Nonrelapse mortality ,business ,Multiple myeloma ,Progressive disease ,030215 immunology ,medicine.drug - Abstract
Background. Autologous stem cell transplantation (ASCT) remains a gold standard treatment for younger patients with multiple myeloma (MM). With the aid of new drugs, the patients live longer and third salvage ASCT is an increasingly used option. However, the outcome of third salvage ASCT has not yet been analyzed. Methods. Between 1997 and 2010, 1288 MM patients who had received at least 3 ASCT were registered in the EBMT database. We excluded patients older than 75 years, those with a time from diagnosis to first ASCT of more than 10 years, patients transplanted with bone marrow, those with a time between relapse and ASCT of less than one month and those with an uncertain relapse date. Planned tandem ASCT was considered to be performed within a 6 month interval and at least 1 month apart. The conditioning regimen for the third transplant was high dosemelphalan alone or in combination withbusulfan orbortezomib. We could distinguish two main groups: 417 patients who received tandem ASCT and then a third ASCT after single relapse (AARA group) and 72 patients who received one ASCT, a second ASCT after first relapse, and a third ASCT after second relapse (ARARA group). A third group, who received tandem ASCT after relapsing following single ASCT comprised only 25 patients and was not studied. Results. We compared the two groups AARA vs ARARA. A third ASCT was performed in the AARA group in more recent years (p=0.047). There were more males than females (65% vs 72%) in both groups (p=NS). The main myeloma isotype was IgG (56% vs 58%). The ISS stage at diagnosis was similar (stage III in 70% vs 72% of cases). The time interval between diagnosis and first ASCT tended to be shorter in the AARA group (p=0.089), being within the first 6 months in 50% vs 38% of patients. The status at third ASCT was different: CR, 5% vs 4%: VGPR or PR, 45% vs 19%: MR or stable disease, 12% vs 15%: primary refractory/progressive disease, 38% vs 62% (p70% at third ASCT was reported in 91% vs 90% of cases. The conditioning regimen at third ASCT was different between the two groups: melphalan 200 mg/m2, 42% vs 18%: melphalan 140 mg/m2, 6%vs 12%: other 52%vs 70% (p=0.018). The median age at third ASCT was 59vs 61 years. There was a trend to a longer time between first ASCT and first relapse (27vs 22 months (p=0.056)) in the AARA group while the interval between first ASCT and third ASCT was much shorter (44vs 64 months (p The median follow-up was similar (70vs73 months (p=0.9)). Engraftment was similar (96%vs93% (p=0.35)).The best response achieved after the third ASCT was superior in the AARA group: CR, 32%vs12%: VGPR or PR, 60%vs71% :MRor SD, 4%vs14%: progression, 4%vs3% (p Conclusions.A third ASCT is feasible in MM with more than 80% of patients achieving at least PR although with increased non relapse mortality. This treatment is mostly used in one of two scenarios: tandem ASCT followed by relapse and a third ASCT, or less commonly a first ASCT followed by a first relapse, a second ASCT, a second relapse and subsequently a third ASCT. The first scenario gives much better results, partly due to a better remission status at the third ASCT with no sign of increased SPM. In this AARA group, if relapse occurred more than 3 years after the initial tandem ASCT, the median OS after third ASCT was more than 4 years. These results should be compared with those obtained with the new drugs, especially in combination. Figure 1. AARAvsARARA groups: Overall Survival after the third transplant Figure 1. AARAvsARARA groups: Overall Survival after the third transplant Figure 2. AARA group: Overall Survival after the third transplant according to the time to relapse following tandem ASCT. Figure 2. AARA group: Overall Survival after the third transplant according to the time to relapse following tandem ASCT. Disclosures Garderet: Takeda: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy. Dreger:Janssen: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Novartis: Consultancy; Gilead: Consultancy; Roche: Consultancy. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Peschel:MophoSys: Honoraria. Meuleman:Bristol-Myers-Squibb: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Ciceri:MolMed SpA: Consultancy. Schönland:Janssen, Prothena, GSK: Consultancy, Employment, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommations, Patents & Royalties, Research Funding, Speakers Bureau. Kröger:Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.
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- 2017
30. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood
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Stephen D. Robinson, Celso Arrais Rodrigues, Jan J. Cornelissen, Vanderson Rocha, Peter Dreger, Carmen Canals, Eliane Gluckman, Arnon Nagler, Pavel Jindra, Mohamad Mohty, Hélène Schoemans, Bernard Rio, Henrik Sengeloev, Dietger Niederwieser, Annalisa Ruggeri, Claudio G. Brunstein, Eefke Petersen, Juergen Finke, Nathalie Fegueux, Anna Sureda, François Guilhot, Hematology, Universidade de São Paulo = University of São Paulo (USP), Hospital Sírio-Libanês, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Heidelberg University Hospital [Heidelberg], University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Rigshospitalet [Copenhagen], Copenhagen University Hospital, University Hospital Freiburg, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), University Medical Center [Utrecht], INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Leipzig, ErasmusMC, Charles University Hospital Pilsen, Chaim Sheba Medical Center, Hôpital Lapeyronie [Montpellier] (CHU), University Hospitals Leuven [Leuven], Avon haematology unit Bristol, Hospital de la Santa Creu i Sant Pau, Addenbrooke's Hospital, Cambridge University NHS Trust, Universidade de São Paulo (USP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Universität Leipzig [Leipzig], and HAL UPMC, Gestionnaire
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Adult ,Male ,[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Cord Blood Stem Cell Transplantation ,Hematopoietic stem cell transplantation ,Lower risk ,Gastroenterology ,Umbilical cord ,Disease-Free Survival ,Risk Factors ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Retrospective Studies ,Neutrophil Engraftment ,business.industry ,Hematopoietic Stem Cell Transplantation ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Articles ,Middle Aged ,3. Good health ,Transplantation ,Survival Rate ,medicine.anatomical_structure ,Cord blood ,Hematologic Neoplasms ,Immunology ,Female ,business ,Unrelated Donors ,Follow-Up Studies - Abstract
on behalf of Eurocord-Netcord and the Lymphoma Working Party and the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation; International audience; We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively; P
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- 2014
31. Long-Term Outcome of Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Waldenstrom Macroglobulinemia (WM)-a Retrospective Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
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Stig Lenhoff, Nathalie Fegueux, Patrice Chevallier, Ariane Boumendil, Charalampia Kyriakou, Dietger Niederwieser, Peter Dreger, Silvia Montoto, Paul Browne, Johannes Schetelig, Didier Blaise, Herve Finel, Charles Craddock, Norbert Schmitz, Stephen Mackinnon, and Henrik Sengeloev
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medicine.medical_specialty ,Performance status ,business.industry ,Immunology ,Waldenstrom macroglobulinemia ,Retrospective cohort study ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,Log-rank test ,Transplantation ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Cumulative incidence ,Rituximab ,Risk factor ,business ,medicine.drug - Abstract
WM is an indolent lymphoma that has benefited from the introduction of novel agents with the achievement of higher response rates. However, WM remains incurable with conventional treatment. In addition, patients with high risk disease have either transient short lived responses or are refractory to conventional treatments. Although international treatment recommendations suggest considering allo-SCT in late relapses or in refractory younger patients, the place and timing of allo-SCT in the treatment algorithm of WM remains unclear. The aim of the present study was to analyse the long-term outcome of allo-SCT in WM. Patients and methods: Eligible for this retrospective study were patients aged 18 years or older who had a first reduced intensity (RIC) or myeloablative (MAC) conditioning allo-SCT (10/10 matched donor, sibling or unrelated) for WM between 2001 and 2013 and were registered with the EBMT. Baseline patient, disease and transplant data were collected from MED-A forms. Centers were requested to provide additional diagnostic, treatment and follow-up information. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, prognostic factors for survival were estimated using Cox regression models and for relapse incidence (IR) and non-relapse mortality (NRM) by Fine and Gray models. Results: 260 patients (72% male) fulfilling the inclusion criteria of this study were identified in the database. The median age was 52 (range 19-72) years. Disease status at allo-SCT was sensitive in 78% and refractory in 22% of the patients. Conditioning was reduced-intensity (RIC) in 66%, with PBSC (92%) being the predominant stem cell source (bone marrow 7%, cord blood 1%). Patients receiving RIC were significantly older and had a longer interval between diagnosis and transplant but were otherwise comparable to patients with myeloablative conditioning (MAC). Donors were related in 65% and unrelated in 35% of the transplants. The median number of treatment lines prior to alloSCT was 3. Pretreatment details were available for 118 patients. Of these, first-line treatment was alkylator-based in 80%, purine analogue (PA)-based in 17%, and contained rituximab in 23%; for 2nd-line treatment, these figures were 50%, 36%, and 34%; and for 3rd-line treatment 41%, 32%, and 44%. Less than 10% of the patients had received bortezomib or imide-based regimens in any pretreatment line. At 100 days the cumulative incidence of acute graft versus host disease (aGVHD) grade I-II was 35%, and grade III-IV was 12%. At 2 years the cumulative incidence of chronic GVHD (cGVHD) was 41%. The development of cGVHD did not significantly impact on any outcome on a landmark analysis. After a median follow-up for living patients of 57 months (IQR 31-97), 5-year NRM, IR, progression-free survival (PFS) and overall survival (OS) were 29%, 24%, 47% and 55%. Risk factor analyses considering age, sex, performance status (PS), disease status, pretreatment lines, rituximab exposure, year of transplant, donor, and conditioning identified PS for NRM, disease status for IR, and PS and MAC for OS as significant predictors of an adverse outcome after multivariable adjustment. Although RIC patients tended to have a lower NRM and a better PFS than MAC patients, this was not statistically significant, suggesting that RIC patients had a better survival after relapse. 45 patients were treated with donor lymphocyte infusions (DLI) and results of DLI were reported in 22 patients. Of these, a response was observed in 60%, which was complete in 55%. Conclusions: This large study demonstrates that allo-SCT can effectively induce long-term disease control in heavily pre-treated patients with WM, suggesting that graft-versus-lymphoma effects are active and stable in WM. Accordingly, DLI seems to be a promising treatment option in case of post-transplant disease recurrence. Additional studies are needed to elaborate the place of allo-SCT in the treatment algorithm of WM in the era of novel agents. Disclosures No relevant conflicts of interest to declare.
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- 2016
32. An EBMT Prospective Non-Interventional Study of Outcomes and Toxicity of Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Patients Previously Treated with Second Generation Tyrosine Kinase Inhibitors
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Liisa Volin, Jennifer Hoek, Slawomira Kyrcz-Krzemien, Arnold Ganser, Mahmoud Aljurf, Henric-Jan Blok, Theo de Witte, Henrik Sengeloev, Arnon Nagler, Eduardo Olavarria, Paul Browne, Mauricette Michallet, Simona Iacobelli, Yves Chalandon, Michael Schleuning, Nicolaus Kröger, Harry C. Schouten, Jakob Passweg, Carmino de Sousa, John A. Snowden, Boris V. Afanasyev, Tamas Masszi, and Gérard Socié
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medicine.medical_specialty ,Immunology ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Prospective cohort study ,Performance status ,business.industry ,Ponatinib ,Imatinib ,Cell Biology ,Hematology ,3. Good health ,Surgery ,Transplantation ,Dasatinib ,Nilotinib ,chemistry ,030220 oncology & carcinogenesis ,business ,Bosutinib ,030215 immunology ,medicine.drug - Abstract
Introduction: Allogeneic stem cell transplantation (SCT) remains a treatment option for patients with chronic myeloid leukemia (CML) that fail to respond to tyrosine kinase inhibitors (TKI). While the use of Imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second generation TKI (2GTKI). We present the results of a prospective non-interventional study (NIS) performed by the European Group for Blood and Marrow Transplantation (EBMT) of all consecutive allogeneic SCT for patients diagnosed with CML from 2009 to 2013. Methods: A prospective follow up of pre and post-transplant data was carried out by the EBMT Leiden office, including TKI therapy data, MED-B and a specific MED-C post transplant data. A total of 94 EBMT centers from 32 countries included 437 patients. Results: We present the results of the 383 patients that fulfilled all the inclusion criteria and had median follow-up of 37 months (1-77). The median age was 45 years (18-68) and 251 (65%) were males. Disease status at the start of 2GTKI was: First chronic phase - CP1 (123, 46%), Accelerated phase or >CP1 (67, 25%) and blast crisis (75, 28%). The choice of 2GTKI was: Dasatinib (155, 40%), Nilotinib (64, 17%) and a sequential combination of Dasatinib/Nilotinib with or without Bosutinib/Ponatinib (164, 43%). In addition, 29% of patients that received Dasatinib were in CP1 at the start of 2GTKI and at the time of SCT compared with 45% at the start and 40% at SCT for patients treated with Nilotinib. For patients that received both TKI in sequential combination, 63% were in CP1 at the start of 2GTKI but only 46% reached the SCT in CP1. Overall disease status at SCT was CP1 in 139 patients (38%), AP in 163 (45%) and BC in 59 (16%). The median interval from diagnosis to SCT was 22 months (2 - 267) and the median interval between starting 2GTKI and SCT was 10 months (1 - 191). The donor was an HLA identical sibling in 130 cases (35%) and unrelated in 244 (65%). The majority of SCT were performed using PBSC (295, 77%), while 272 (71%) were myeloablative and 111 (29%) reduced intensity conditioning. The EBMT score was low (0-2) in 26 (7%), intermediate (3-4) in 216 (62%) and high (5-7) in 107 (31%). Primary graft failure (PGF) occurred in 10 (3%) cases, while the incidence of acute GVHD was 34% (95% CI 29-39) and chronic GVHD (CGVHD) was 60% at 5 years (95% CI 54-66). CGVHD occurred at a median of 5.7 months (3-61) post SCT. Other post SCT complications included veno-occusive disease of the liver (VOD) in 6 cases (2%) and severe infection in 195 (65%). There were no differences in post-transplant complications amongst the 3 different 2GTKI subgroups. Overall non-relapse mortality was 18% (95% CI 14-22) at 12 months and 24% (95% CI 19-29) at 5 years. Relapse incidence was 36% (95% CI 29-42), overall survival was 56% (95% CI 50-62) and relapse-free survival was 40% (95% CI 33-47) at 5 years. Overall survival was 67% (95% CI 59-75) at 5 years for patients in CP1. No differences in post-transplant outcomes were found amongst the 3 different 2GTKI subgroups. However, the EBMT score, performance status and disease stage at 2GTKI and at SCT were predictive of overall and progression-free survival. Discussion: This prospective study demonstrates the feasibility of performing allogeneic SCT in CML patients previously treated with 2GTKI. The rate of post-transplant complications including graft failure, VOD, infections, GVHD and non-relapse mortality seems comparable to that of patients treated with Imatinib or TKI-naïve. We observed no differences between outcomes for patients receiving Dasatinib, Nilotinib or any other combination of 2GTKI (including Bosutinib and Ponatinib) pre-SCT. However, patients receiving Dasatinib were more likely to proceed to SCT in advanced phase than in CP1. Patients in CP1 have a very good overall survival despite prior treatment with 2GTKI. Of note, even after 2GTKI, the EBMT score remains a strong predictor of overall and disease-free survival for CML patients undergoing allogeneic SCT. Disclosures Schouten: Sanofi: Consultancy; Novartis: Consultancy. de Witte:Novartis: Honoraria, Research Funding; Celgene: Consultancy; Incyte: Consultancy. Kröger:Neovii: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.
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- 2016
33. Impact of Different In Vivo T Cell Depletion Strategies on Outcomes Following Hematopoietic Stem Cell Transplantation for Idiopathic Aplastic Anaemia: A Study on Behalf of the EBMT SAA Working Party
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Stephen D. Robinson, Judith C. W. Marsh, Antonio M. Risitano, Dietrich W. Beelen, Gérard Socié, Mickey Koh, Jean-Hugues Dalle, Joan Hendrik Veelken, Simona Iacobelli, Cora Knol, John A. Snowden, Sujith Samarasinghe, Andrea Bacigalupo, Rose-Marie Hamladji, Didier Blaise, Mahmoud Aljurf, Ghulam J. Mufti, Carlo Dufour, and Henrik Sengeloev
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Off-label use ,Biochemistry ,Surgery ,Transplantation ,Regimen ,Graft-versus-host disease ,Median follow-up ,Internal medicine ,medicine ,Alemtuzumab ,Stem cell ,business ,medicine.drug - Abstract
To determine the optimal serotherapy regimen in idiopathic aplastic anaemia stem cell transplantation, we analysed 1837 patients who underwent either in vivo T cell depletion with either ATG (n=1283) or Alemtuzumab (n=261) or no serotherapy (n=293) as part of their conditioning regimen. All patients had either undergone a matched sibling or matched unrelated donor stem cell transplant (at least 6 out of 6). Data was obtained retrospectively from the EBMT SAA database, between the periods 2000-2013. The major endpoints were graft versus host disease, overall survival and event free survival. Events were classified as graft failure, secondary malignancy, relapse and requirement for second transplant. The median follow up was 34 months in the ATG group, 30.9 months in the Alemtuzumab group and 47.9 months in the no serotherapy group. Rate of grade 2-4 acute GVHD was 19.1% without serotherapy; this was higher than that observed with both ATG (13.3%, p Figure 1. Figure 1. Disclosures Snowden: Celgene: Other: Educational support, Speakers Bureau; Janssen: Other: Educational support, Speakers Bureau; MSD: Consultancy, Other: Educational support, Speakers Bureau; Sanofi: Consultancy. Dufour:Pfizer: Consultancy. Risitano:Pfizer: Consultancy; Novartis: Research Funding; Rapharma: Consultancy, Research Funding; Alnylam: Consultancy, Research Funding; Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: this paper includes discussion of the use of alentuzumab for GVHD prophylaxis, which is currently off-label.
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- 2015
34. Double Cord Blood Transplantation: Incidence, Organ Involvement and Risk Factors of Acute Graft Versus Host Disease. a Retrospective Analysis on Behalf of Eurocord, ALWP and Cqwp-EBMT
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Johanna Tischer, Annalisa Ruggeri, Jean-Henri Bourhis, Dimitrios Karakasis, Laurence Clement, Eric Deconinck, Patrice Chevallier, Mohamad Mohty, Mauricette Michallet, Henrik Sengeloev, Chantal Kenzey, Myriam Labopin, Eefke Petersen, Jan J. Cornelissen, Erick Xavier, Charles Craddock, Gérard Socié, Fernanda Volt, Thierry Lamy, Arnon Nagler, Lionel Mannone, Didier Blaise, Natacha Maillard, Noel Milpied, Rafael F. Duarte, Jean-Yves Cahn, Federica Giannotti, Vanderson Rocha, Eliane Gluckman, Jacques-Olivier Bay, Nathalie Fegueux, and Grant McQuaker
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medicine.medical_specialty ,Acute leukemia ,Cyclophosphamide ,business.industry ,Incidence (epidemiology) ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Surgery ,Transplantation ,Regimen ,Graft-versus-host disease ,Internal medicine ,medicine ,Cumulative incidence ,Prospective cohort study ,business ,medicine.drug - Abstract
Double umbilical cord blood transplantation (dUCBT) has extended the applicability of UCBT for hematologic disorders especially to adult patients (pts) for whom the low cellular content of a single unit is a limiting factor. However the use of dUCBT has been, recently, associated with a higher incidence of acute graft-versus-host disease (aGVHD) when compared with single UCBT (sUCBT). Moreover, several retrospective and prospective studies have addressed risk factors for aGVHD with some conflicting results. Whether the number of total nucleated cells, HLA disparities, type of conditioning regimen or GVHD prophylaxis have an impact on aGVHD incidence in dUCBT is yet to be established in a larger series of patients. With this background, this report analyzed 921 adult recipients who underwent dUCBT for hematologic malignancies from 2005-2012 in EBMT centers. Median age was 46 (range, 18-72) years (yrs) and 59% were males. Diagnosis was acute leukemia in 56%, MDS/CML in 19% and lymphoid malignancies in 25%; 22% of pts received at least one prior autologous HSCT. Reduced-intensity conditioning (RIC) was used in 68% of pts and the most common regimen for both myeloablative conditioning (MAC) and RIC was Cyclophosphamide-Fludarabine-TBI (TCF) (40% and 78%, respectively). ATG was used in 30% of pts. GVHD prophylaxis consisted of a MMF based regimen in 774 pts (84%); cyclosporine±steroids in 103 (11%) and MTX-based regimen in 44 (5%). HLA incompatibilities were classified using the cord blood unit bearing the highest degree of mismatch with the recipient: 1% were HLA matched 6/6, 25% were 5/6, 67% were 4/6, and 7% With a median follow-up of 26 months (range, 3-98) aGVHD was absent in 418 patients (46%), 169 pts developed grade I (18%), 194 grade II (21%), 103 grade III (11%) and 37 grade IV (4%). One-hundred day cumulative incidence (CI) of aGVHD grade II-IV was 36%±2% and III-IV 15%±2%, with a median time of onset of 28 days (range, 4-97). Of those pts with grade II-IV aGVHD, 82% had skin, 66% gastro-intestinal tract (GIT) and 25% liver involvement. The most common organ involvement in pts with grade III-IV aGVHD was GIT (89%) followed by skin (71%) and liver (39%). Treatment of grade II-IV aGVHD was steroid alone in 91% of pts. For pts with grade III-IV aGVHD steroid was used alone in 77% of pts, 11% received steroid+monoclonal antibodies, 3% steroid+MTX and 9% other treatments (figure 1). At day 60, CI of neutrophil engraftment was 84%. Out of the 712 pts at risk, 218 developed chronic GVHD (cGVHD) with a CI at 2 yrs of 25%±5%. Of these, 102 pts (47%) had previous aGVHD grade II-IV and 116 (53%) had de novo cGVHD. CI of early NRM (at day 100) was 13%. At 2 yrs, the probability of PFS was 37%, NRM 35% and relapse 28%. In multivariate analysis, the following factors were associated with an increased incidence of grade II-IV GVHD: use of MAC (HR: 1.45 (1.12-1.91), p=0.005), absence of ATG (HR: 2.39 (1.78-3.30), p Despite previous analysis showing increased incidence of acute and chronic GVHD after dUCBT, our study demonstrated that the GVHD incidence remains relatively low in dUCBT setting when compared to published data on HLA matched adult donor. In pts developing grade II-IV aGVHD, skin was the most common organ affected, followed by GIT and liver. Steroid alone was the backbone treatment of aGVHD and the association of steroid and other therapies (mainly monoclonal antibodies) was mostly seen in pts affected by grade III-IV aGVHD. Acute GVHD grade II-IV seems to be influenced by the intensity of the conditioning regimen, the use of ATG, and HLA compatibility; therefore prospective trials evaluating the role of these factors in dUCBT should be addressed. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
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- 2014
35. 1168Use of First Positive Cytomegalovirus (CMV) PCR Determination to Differentiate a Viral Blip From Established CMV Infection in Transplant Recipients
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Finn Gustafsson, Henrik Sengeloev, Jens D Lundgren, Martin Iversen, Lars Vindeloev, Søren Schwartz Sørensen, Caspar da Cunha-Bang, Nikolai Kirkby, Allan Rasmussen, and Isabelle Paula Lodding
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Pathology ,medicine.medical_specialty ,Infectious Diseases ,Oncology ,business.industry ,Congenital cytomegalovirus infection ,Medicine ,business ,medicine.disease ,Virology - Published
- 2014
36. Current Outcome Of HLA Identical Sibling Vs Unrelated DONOR Transplants In Severe Aplastic Anemia : An EBMT Analysis
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Andrea Bacigalupo, Rosi Oneto, Judith C. W. Marsh, Carlo Dufour, Ali Ünal, Mahmoud Aljurf, Anna Locasciulli, Jakob Passweg, Rose-Marie Hamljadi, Gérard Socié, Slawomira Kyrcz-Krzemien, Henrik Sengeloev, Dietrich W. Beelen, A Cybicka, and A Mashan
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medicine.medical_specialty ,business.industry ,Immunology ,Confounding ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,Graft-versus-host disease ,medicine.anatomical_structure ,Cord blood ,Internal medicine ,Cohort ,medicine ,Cumulative incidence ,Bone marrow ,Sibling ,Aplastic anemia ,business - Abstract
Background Unrelated donor (UD) transplants for patients with acquired severe aplastic anemia (SAA) have been known to yield inferior results when compared to transplants from HLA identical siblings (SIB). With the significant improvement of UD transplants over the past decade, on may ask whether this is still true. Aim of the study To compare the outcome of UD with SIB transplants in recent cohort of patients reported to the European Group for Blood and Marrow Transplantation (EBMT) Aplastic Anemia Registry. Patients We have analyzed 1500 patients with acquired aplastic anemia (SAA), who received a first bone marrow (BM) or peripheral blood (PB),. HLA matched transplant between 2005 and 2009, from identical siblings (n=975) or unrelated donors (n=525). Excluded were cord blood grafts. Clinical characteristics of the two groups were different: although SIB vs UD grafts had comparable age (20 vs 21 years median age , p=0.1), SIB grafts were performed earlier (152 vs 607 median days from diagnosis, p Results The cumulative incidence (CI) of engraftment was 91% for both SIB and UD transplants; and the CI of acute GvHD grade II-IV was11% in SIB and 25% in UD grafts (p In multivariate COX analysis the strongest negative predictors of survival was the use of PB as a stem cell source (RR 2, p20 years (RR 2.0, p180 days (RR 1.3, p=0.006) and no anti-thymocyte globulin (ATG) in the conditioning (RR 1.6, p=0.002). The use of an UD as compared to a SIB was not statistically significant (RR 1.2, p=0.4). When stratified for negative predictors, the actuarial 5 year survival of SIB and UD transplants was 91% vs 81% in low risk patients (n=541, 0-1 negative predictors, p=0.052), 74% vs 72% for the largest group of intermediate risk patients (n=829, 2-3 negative predictors, p=0.4) and 53% vs 50% for a small group of high risk patients (n=130, 4 negative predictors, p=0.8). Conclusions This study suggests that the outcome of UD and SIB transplant for SAA is currently comparable, if one corrects for confounding variables, and especially time to transplant. This information warrants the activation of an unrelated donor search for all patients lacking an HLA matched sibling, up to the age of 60, and this may be relevant for treatment strategies. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2013
37. Impact of Postremission Consolidation Chemotherapy On Outcome After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for AML in First Complete Remission (CR1): A Report From the Acute Leukemia Working Party of EBMT
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Arnon Nagler, Mohamad Mohty, Jan J. Cornelissen, Patrice Chevallier, Didier Blaise, J. Kuball, Lars Vindeløv, Myriam Labopin, Moshe Yeshurun, and Henrik Sengeloev
- Subjects
medicine.medical_specialty ,Acute leukemia ,business.industry ,Immunology ,Retrospective cohort study ,Consolidation Chemotherapy ,Context (language use) ,Cell Biology ,Hematology ,Biochemistry ,Transplantation ,Internal medicine ,Cohort ,Cytarabine ,Medicine ,Cumulative incidence ,business ,medicine.drug - Abstract
Abstract 3098 The role of consolidation therapy after successful remission induction is well established in the treatment paradigm of patients with AML in the non-transplant setting. Most contemporary treatment protocols for young AML patients not transplanted in CR1 include repetitive cycles of high-dose cytarabine. However, in the standard myeloablative allo-SCT setting, consolidation therapy prior to transplant did not prove to have a beneficial impact on overall survival (OS), leukemia free survival (LFS) or relapse incidence (RI) as shown in 2 previous studies from the IBMTR and EBMT. In the context of RIC and non-myeloablative (NMA) allo-SCT, this picture might be different since one may speculate that consolidation therapy prior to transplantation may allow for reducing the incidence of relapse while waiting for the GVL effect. Nevertheless, the value of consolidation prior to RIC and NMA allo-SCT in AML in CR1 has not yet been explored. Thus, this multicenter retrospective analysis aimed to assess the role of consolidation prior to RIC/NMA allo-SCT in a cohort of AML CR1 patients (n=789) who received HLA-identical (n=564) or MUD (n=225) peripheral blood stem cell grafts between 2000 and 2010 and who were reported to the EBMT registry. Patients who required more than 2 cycles of induction to achieve CR were excluded. In this cohort, 591 patients received at least one course of consolidation and 198 patients did not receive any consolidation before SCT. With a median follow-up of 40 months (range, 1–140), the Kaplan-Meier estimates of OS and LFS at 3 years were 55% (95%CI, 52–59%) and 52% (95%CI, 48–55%), respectively. The cumulative incidence of relapse was 33% (95%CI, 29–36%). The median time from CR to allo-SCT was longer among patients who received consolidation compared with patients who received no consolidation (4.7 vs. 2.2 months; p With this background, we elected to focus on the group of 373 patients who were transplanted within the median time frame between CR achievement and allo-SCT (3 months for sibling donors and 4 months for MUDs). In this subgroup, 151 did not receive any consolidation and 222 received ≥1 consolidation (1 course, n=164, ≥ 2 courses, n=58).Patients who did not receive any consolidation were older (58 vs. 56 y, p=0.03), had a shorter time from CR to transplantation (56 vs. 71 days, p In all, this retrospective study did not find any impact of postremission consolidation on outcome of patients with AML in CR1 who underwent allo-SCT with reduced-intensity or NMA conditioning. However, further investigation of high-risk subpopulations and well designed prospective controlled studies are warranted. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
38. Extramedullary Leukemia and Myeloid Sarcoma in AML: Results From a Population-Based Registry Study of 2261 Patients
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Marianne Tang Severinsen, Jan Maxwell Nørgaard, Lone S. Friis, Eigil Kjeldsen, Lars Kjeldsen, Henrik Sengeloev, Mette Holm, Ove Juul Nielsen, Hans Erik Johnsen, Morten K. Jensen, Olav J. Bergmann, and Lene Sofie Granfeldt Oestgaard
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Oncology ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,Transplantation ,Leukemia ,medicine.anatomical_structure ,Statistical significance ,Internal medicine ,Cohort ,medicine ,Myeloid sarcoma ,Bone marrow ,Progression-free survival ,business ,education - Abstract
Abstract 2003 The prognosis of patients suffering from AML with manifestations of accompanying extramedullary leukemia (EML) including myeloid sarcoma (MS) compared to that of AML patients not exhibiting EML manifestations is still an open question as results from previous studies have been contradictory most likely due to selection bias. Here we present an analysis performed in a cohort of 2261 patients representing >90% of all AML patients diagnosed and treated in Denmark during the eleven-year period January 2000 through December 2010. The goal was to investigate the prognostic impact of presence of EML at time of AML diagnosis by a retrospective population- and registry-based analysis Of these patients, 219 (9.7%) showed signs of EML at time of AML presentation. Anatomic sites of EML were: lymph nodes (3.0%), skin (2.7%), spleen (1.7%), oral (1.3%), CNS (0.4%), testes (0.2%), other sites (1.1%), and two or more anatomical sites (0.5%). In 27 cases myeloid sarcoma was not accompanied by AML in the bone marrow and, thus, presented as isolated MS. In total, 1168 of the 2261 (52 %) patients were treated with curative intention. Allogeneic stem cell transplantation (Standard allo in 105 cases, and reduced intensity conditioning (RIC) transplant in 90 cases) was conducted in a total of 195 patients (118 in CR1, 65 in CR2, and 12 during other disease stages). Overall the frequencies of allogeneic transplantations in curatively treated patients were 13.7% in patients with EML and 8.5% in patients without EML. The presence of EML at time of leukemia diagnosis had no statistical significance to probability of obtaining complete remission (CR), nor to duration of overall survival (OS) (Table 1. and Fig. 1). By contrast, well-established prognostic parameters such as presenting cytogenetic abnormalities (categorized according to revised MRC-criteria, D. Grimwade et al. Blood, 2010), age, leukocyte count, and type of leukemia (secondary vs de novo) were all found to be statistically significant to probability of attainment of (CR) and to duration of OS in uni- as well as multivariate analyses. Gender was of borderline statistical significance with respect to probability of attainment of CR and to OS (Table 1).Figure 1Years from AML diagnosisPatients with EML(n = 132)Patients without EML(n = 1007)p-value (log-rank test) = 0.51Figure 1. Years from AML diagnosis. / Patients with EML. / (n = 132). / Patients without EML. / (n = 1007). / p-value (log-rank test) = 0.51Table 1.Factors of significance to probability of attainment of CR and to overall survival (OS)Probability of CR (Logistic regression, nevaluable = 927)Probability of overall survival (Cox regression, nevaluable = 958)VariableOdds ratio (OR)95% CI of ORP valueHazard ratio95% CI of HRP valueEML––0.82––0.54Age1.061.04–1.08 Additionally, patients with EML at leukemia presentation who were subjected to an allogeneic stem cell transplantation had a prognosis no different from that of AML patients not exhibiting signs of EML (Fig.2). Analyses of progression free survival are ongoing and will be presented at the meeting.Figure 2Years from AML diagnosisPatients without EML(n = 165)Patients with EML(n = 30)p-value (log-rank test) = 0.75Figure 2. Years from AML diagnosis. / Patients without EML. / (n = 165). / Patients with EML. / (n = 30). / p-value (log-rank test) = 0.75 From this analysis we conclude that presence of EML does not predict for an inferior CR-rate or for shorter survival in AML. We find no clear justification for a more aggressive therapeutic approach or performance of allogeneic stem cell transplantation in AML patients with EML. Therapeutic decisions should be guided by other prognostic parameters, e.g., age and cytogenetic aberrations which are of far greater importance than the presence of EML. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2011
39. Graft-Versus-Leukemia (GVL) Effect After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) as Treatment for Acute Myeloid Leukemia (AML): a Survey From the Acute Leukemia Working Party of the EBMT
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Noel-Jean Milpied, Jan J. Cornelissen, Nadezda Basara, Didier Blaise, Claes Malm, Dietger Niederwieser, Frédéric Baron, Gérard Socié, Vanderson Rocha, Henrik Sengeloev, Jeroen Janssen, Mohamad Mohty, Myriam Labopin, and Eefke Petersen
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Oncology ,medicine.medical_specialty ,Acute leukemia ,business.industry ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Lower risk ,medicine.disease ,Biochemistry ,Transplantation ,Regimen ,Leukemia ,surgical procedures, operative ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Alemtuzumab ,business ,Busulfan ,medicine.drug - Abstract
Abstract 3313 Poster Board III-201 RIC allo-SCT has been increasingly used as treatment for AML patients (pts) ineligible for myeloablative allo-SCT. Previous studies have observed a lower risk of relapse in pts who experienced chronic GVHD after RIC allo-SCT versus in those who did not. The objective of the current study was to further investigate the association between chronic GVHD and relapse in a large cohort of pts given RIC allo-SCT as treatment for AML. Data from 1188 AML pts in first or second CR transplanted between 2000 and 2008 following a RIC regimen at EBMT affiliated centers were analyzed. Patients were given PBSC from HLA-identical sibling (MRD, n=879), or from HLA-matched unrelated donors (MUD, n=309). RIC was defined as Busulfan conditioning regimens containing ≤ 8mg/kg total dose, or TBI 55 yrs (P=.008), alemtuzumab use in the RIC (P=.048), TBI-based RIC (P=.006), high-risk cytogenetics (P=.001), and absence of chronic GVHD (P=.015) were each associated with higher risk of relapse. Factors associated with high NRM were MUD versus MRD (P=.003), grade II-IV acute GVHD (P 55 yrs (P=.007), alemtuzumab use in the RIC (P=.012), and high-risk cytogenetics (P=.003). In conclusion, in this cohort of AML patients transplanted in remission, chronic GVHD was associated with a lower risk of relapse while profound in-vivo T cell depletion with alemtuzumab was associated with higher relapse rate suggesting that GVL effects play a role in preventing AML relapse in patients given RIC allo-SCT. Therefore, closed surveillance of patients in this setting not presenting chronic GVHD such as decreasing of immunosuppression should be further investigated. Disclosures No relevant conflicts of interest to declare.
- Published
- 2009
40. Comparison of Low Dose Total Body Irradiation (TBI)-Based Reduced Intensity Conditioning (RIC) Vs. Chemotherapy-Based RIC Prior to Allogeneic Stem Cell Transplantation (allo-SCT) From An HLA Identical Sibling Donor for Acute Myeloid Leukemia (AML) in First Complete Remission (CR1): a Retrospective Analysis of 1200 Patients From the Acute Leukemia Working Party of EBMT
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Vanderson Rocha, Henrik Sengeloev, Ghulam J. Mufti, Noel-Jean Milpied, Jan J. Cornelissen, Didier Blaise, Arnon Nagler, Myriam Labopin, Eefke Petersen, John G. Gribben, Mohamad Mohty, Hakan Goker, and Jeroen Janssen
- Subjects
Oncology ,medicine.medical_specialty ,Acute leukemia ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Total body irradiation ,medicine.disease ,Biochemistry ,Bone marrow purging ,Fludarabine ,Surgery ,Transplantation ,Leukemia ,Regimen ,hemic and lymphatic diseases ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Abstract 1190 Poster Board I-212 RIC is increasingly used in allo-SCT for AML patients. RIC allo-SCT represents an attempt to harness the immune graft-versus-leukemia effect while attempting to control or overcome toxicity. Most of the RIC protocols have been shown to be highly immunosuppressive, but because of the variability in the degree of myeloablation, the toxicity and efficacy profiles might vary from one protocol to another. Low dose TBI in RIC is frequently used, however it is still unknown whether outcomes are different when comparing low dose TBI-based RIC and chemotherapy-based RIC regimens. Moreover, some transplant centres do not have radiation facilities. Therefore, the aim of this study was to compare outcomes (leukemia-free survival: LFS, Non-Relapse Mortality: NRM, and relapse incidence) between patients receiving a low dose TBI-based RIC vs. chemotherapy-based RIC prior to allo-SCT from an HLA identical sibling donor for AML in CR1. Between 2000 and 2008, 323 patients with AML in CR1 were treated with low dose TBI-based RIC (Fludarabine + TBI) and 877 received a chemotherapy-based RIC (including fludarabine in the majority of cases), and reported to the EBMT Registry. All patients received allogeneic PBSC from HLA-identical sibling donors. Patients receiving TBI-based RIC were older (median 56 y. vs. 54 y.; p The median time to engraftment (ANC>500/μL) was comparable between both groups (15 vs. 16 days, p=NS). With a median follow-up of 15 (range, 0.3-107) months, 2 years LFS were 50±3%, 53±2% in the TBI-based RIC and chemo based RIC groups respectively (p=0.16). Also, at 2 years, the relapse incidence was not significantly associated with the type of RIC regimen: 37±3%, 34±2% in the TBI-based RIC and chemo-based RIC groups respectively (p=0.17). Finally, NRM was also comparable between both groups [21±3% and 20±2% in the TBI-based RIC and chemo-based RIC groups respectively; p=0.60) Despite its retrospective nature, results from this large study suggest that RIC allo-SCT is a valid option for AML patients not eligible for standard allo-SCT. The overall outcomes (LFS, NRM and relapse) appear not to be significantly different between AML patients in CR1 receiving a low dose TBI-based RIC allo-SCT versus those receiving a chemotherapy-based RIC allo-SCT using an HLA-identical sibling donor. Disclosures: No relevant conflicts of interest to declare.
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