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1. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study

Author

Peters, Christina, Dalle, Jean-Hugues, Locatelli, Franco, Poetschger, Ulrike, Sedlacek, Petr, Buechner, Jochen, Shaw, Peter J, Staciuk, Raquel, Ifversen, Marianne, Pichler, Herbert, Vettenranta, Kim, Svec, Peter, Aleinikova, Olga, Stein, Jerry, Güngör, Tayfun, Toporski, Jacek, Truong, Tony H, Diaz-de-Heredia, Cristina, Bierings, Marc, Ariffin, Hany, Essa, Mohammed, Burkhardt, Birgit, Schultz, Kirk, Meisel, Roland, Lankester, Arjan, Ansari Djaberi, Marc Georges, Schrappe, Martin, von Stackelberg, Arend, Balduzzi, Adriana, Corbacioglu, Selim, Bader, Peter, IBFM Study Group, IntReALL Study Group, I-BFM SCT Study Group, EBMT Paediatric Diseases Working Party, Peters, C, Dalle, J, Locatelli, F, Poetschger, U, Sedlacek, P, Buechner, J, Shaw, P, Staciuk, R, Ifversen, M, Pichler, H, Vettenranta, K, Svec, P, Aleinikova, O, Stein, J, Güngör, T, Toporski, J, Truong, T, Diaz-de-Heredia, C, Bierings, M, Ariffin, H, Essa, M, Burkhardt, B, Schultz, K, Meisel, R, Lankester, A, Ansari, M, Schrappe, M, von Stackelberg, A, Balduzzi, A, Corbacioglu, S, Bader, P, HUS Children and Adolescents, University Management, Lastentautien yksikkö, and Children's Hospital

Subjects
Male, Oncology, Cancer Research, Lymphoblastic Leukemia, medicine.medical_treatment, Hematopoietic stem cell transplantation, law.invention, 0302 clinical medicine, Randomized controlled trial, 3123 Gynaecology and paediatrics, Busulfan / analogs & derivatives, law, Antineoplastic Combined Chemotherapy Protocols, TBI, Child, Childhood all, Etoposide, Busulfan / administration & dosage, Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy, ddc:618, Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology, Chemoradiotherapy, ORIGINAL REPORTS, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Total body irradiation, Prognosis, 3. Good health, Survival Rate, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Child, Preschool, 030220 oncology & carcinogenesis, HSCT, hematopoietic stem cell transplantation, Chemoradiotherapy / mortality, Female, Vidarabine, Whole-Body Irradiation, medicine.medical_specialty, Adolescent, 3122 Cancers, Vidarabine / analogs & derivatives, acute lymphoblastic leukemia, Equivalence Trials as Topic, 03 medical and health sciences, Internal medicine, Antineoplastic Combined Chemotherapy Protocols / therapeutic use, Hematologic Malignancy, medicine, Humans, Busulfan, Survival rate, childhood, Chemotherapy, business.industry, International Agencies, Thiotepa / administration & dosage, Clinical trial, Etoposide / administration & dosage, Vidarabine / administration & dosage, Whole-Body Irradiation / mortality, business, Literatur Kommentiert, total body irradiation, Thiotepa, Follow-Up Studies, 030215 immunology
Abstract

PURPOSE Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients. PATIENTS AND METHODS FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129 ). RESULTS Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively. CONCLUSION Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.

Published
2021

2. Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy

Author

Tourret, Marie, Talvard-Balland, Nana, Lambert, Marion, Ben Youssef, Ghada, Chevalier, Mathieu F, Bohineust, Armelle, Yvorra, Thomas, Morin, Florence, Azarnoush, Saba, Lantz, Olivier, Dalle, Jean-Hugues, and Caillat-Zucman, Sophie

Subjects
Adult, Male, Immune Cell Therapies and Immune Cell Engineering, Adolescent, Infant, Newborn, Infant, Adaptive Immunity, Middle Aged, adoptive, Mucosal-Associated Invariant T Cells, Young Adult, Child, Preschool, Humans, Female, Immunotherapy, transplantation immunology, Child, Aged
Abstract

Background Mucosal-associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of antimicrobial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during the infancy. The cytotoxic potential of MAIT cells, as well as their newly described regulatory and tissue repair functions, open the possibility of exploiting their properties in adoptive therapy. A prerequisite for their use as ‘universal’ cells would be a lack of alloreactive potential, which remains to be demonstrated. Methods We used ex vivo, in vitro and in vivo models to determine if human MAIT cells contribute to allogeneic responses. Results We show that recovery of MAIT cells after allogeneic hematopoietic stem cell transplantation recapitulates their slow physiological expansion in early childhood, independent of recovery of non-MAIT T cells. In vitro, signals provided by allogeneic cells and cytokines do not induce sustained MAIT cell proliferation. In vivo, human MAIT cells do not expand nor accumulate in tissues in a model of T-cell-mediated xenogeneic graft-versus-host disease in immunodeficient mice. Conclusions Altogether, these results provide evidence that MAIT cells are devoid of alloreactive potential and pave the way for harnessing their translational potential in universal adoptive therapy overcoming barriers of HLA disparity. Trial registration number ClinicalTrials.gov number NCT02403089.

Published
2021

3. Bone Mineral Density Evolution and Its Determinants in Long-term Survivors of Childhood Acute Leukemia

Author

Tabone, Marie-Dominique, Kolta, Sami, Auquier, Pascal, Vercasson, Camille, Chastagner, Pascal, Kanold, Justyna, Rohrlich, Pierre-Simon, Bertrand, Yves, Baruchel, André, Plantaz, Dominique, Gandemer, Virginie, Ducassou, Stéphane, Petit, Arnaud, Paillard, Catherine, Leverger, Guy, Dalle, Jean-Hugues, Berbis, Julie, Roux, Christian, and Michel, Gérard

Subjects
lcsh:RC633-647.5, lcsh:Diseases of the blood and blood-forming organs, Article
Abstract

This prospective study aimed to analyze determinants that can influence bone mineral density evolution in childhood acute leukemia survivors. Patients included were selected from the long-term follow-up LEA cohort and had dual energy radiograph absorptiometry scan between 10 and 18 years and after the age of 18. All scans were centrally reviewed. Bone mineral density was measured at the lumbar spine, femoral neck, total hip, and whole body, and expressed as z-score. Eighty-nine patients (female 39, lymphoblastic leukemia 68, relapse 25, hematopoietic stem cell transplantation 44, and mean age 15.4 and 20.1 years at the first and second scans, respectively) were studied. The first and second scan z-scores were significantly correlated (P < 10−3). Mean femoral neck and total hip z-scores improved significantly between the first and second scans, whereas no significant evolution occurred at the lumbar spine and whole-body level. On the second evaluation, 14.6% of patients had z-score

Published
2021

5. ABO incompatibile graft management in pediatric transplantation

Author

Balduzzi, Adriana, Bönig, Halvard, Jarisch, Andrea, Nava, Tiago, Ansari Djaberi, Marc Georges, Cattoni, Alessandro, Prunotto, Giulia, Lucchini, Giovanna, Krivan, Gergely, Matic, Toni, Kalwak, Krzyzstof, Yesilipek, Akif, Ifversen, Marianne, Svec, Peter, Buechner, Jochen, Vettenranta, Kim, Meisel, Roland, Lawitschka, Anita, Peters, Christina, Gibson, Brenda, Dalissier, Arnaud, Corbacioglu, Selim, Willasch, André, Dalle, Jean-Hugues, Bader, Peter, EBMT Pediatric Diseases Working Party, Balduzzi, A, Bönig, H, Järisch, A, Nava, T, Ansari, M, Cattoni, A, Prunotto, G, Lucchini, G, Krivan, G, Matic, T, Kalwak, K, Yesilipek, A, Ifversen, M, Svec, P, Büchner, J, Vettenranta, K, Meisel, R, Lawitschka, A, Peters, C, Gibson, B, Dalissier, A, Corbacioglu, S, Willasch, A, Dalle, J, Bader, P, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, and Helsinki University Hospital Area

Subjects
medicine.medical_specialty, Erythrocytes, BONE-MARROW, medicine.medical_treatment, Pure red cell aplasia, Hematopoietic stem cell transplantation, Hemolysis, Isohemagglutinin, ABO Blood-Group System, ABO incompatibility, 03 medical and health sciences, 0302 clinical medicine, TRANSFUSION, 3123 Gynaecology and paediatrics, ABO blood group system, medicine, Humans, Child, Bone Marrow Transplantation, Transplantation, ddc:618, PLASMA, business.industry, Hematology, medicine.disease, 3. Good health, Surgery, REDUCTION, medicine.anatomical_structure, pediatric, Tolerability, Blood Group Incompatibility, 030220 oncology & carcinogenesis, hematopoietic stem cell transplantation, Erythropoiesis, PROGENITOR-CELL TRANSPLANTATION, Bone marrow, DEPLETION, business, 030215 immunology
Abstract

Up to 40% of donor-recipient pairs in SCT have some degree of ABO incompatibility, which may cause severe complications. The aim of this study was to describe available options and survey current practices by means of a questionnaire circulated within the EBMT Pediatric Diseases Working Party investigators. Major ABO incompatibility (donor's RBCs have antigens missing on the recipient's cell surface, towards which the recipient has circulating isohemagglutinins) requires most frequently an intervention in case of bone marrow grafts, as immediate or delayed hemolysis, delayed erythropoiesis and pure red cell aplasia may occur. RBC depletion from the graft (82%), recipient plasma-exchange (14%) were the most common practices, according to the survey. Graft manipulation is rarely needed in mobilized peripheral blood grafts. In case of minor incompatible grafts (donor has isohemagglutinins directed against recipient RBC antigens), isohemagglutinin depletion from the graft by plasma reduction/centrifugation may be considered, but acute tolerability of minor incompatible grafts is rarely an issue. According to the survey, minor ABO incompatibility was either managed by means of plasma removal from the graft, especially when isohemagglutinin titer was above a certain threshold, or led to no intervention at all (41%). Advantages and disadvantages of each method are discussed.

Published
2021

6. Allogeneic Hematopoietic Stem Cell Transplantation for BCR/ABL1-Negative Myeloproliferative Neoplasms in Children - Retrospective Report on Behalf of I-BFM SCT Committee and EBMT Pediatric Diseases WP

Author

Patrick, Katharine, Gruhn, Bernd, Corbacioglu, Selim, Kupesiz, Alphan, Balduzzi, Adriana, Al-Seraihy, Amal, Wynn, Robert, Veys, Paul, Stepensky, Polina, Robinson, Stephen, Locatelli, Franco, Dalissier, Arnaud, Galimard, Jacques-Emmanuel, Wachowiak, Jacek, Tbakhi, Abdelghani, Diaz, Miguel Angel, Socie, Gerard, Sedlacek, Petr, Abboud, Miguel, Beelen, Dietrich, Krivan, Gergely, ÜNAL, ALİ, Bodova, Ivana, Freycon, Claire, Dalle, Jean-Hugues, Jubert, Charlotte, Ferster, Alina, Ifversen, Marianne, and Hamladji, Rose-Marie

Published
2020

7. Adoptive immunotherapy of refractory viral infections after allogeneic HSCT: An academic network framing the use of ATMP under hospital exemption

Author

Wang, Yingying, De Carvalho-Bittencourt, Marcelo, Pierre, Typhaine, Gauthier, Melanie, Decot, Veronique, Clement, Laurence, Pochon, Cecile, Bilger, Karine, Larghero, Jerome, Rouard, Hélene, Legendre, Anne, Petitpain, Nadine, Dalle, Jean Hugues, Bensoussan, Danièle, unité de thérapie cellulaire et Tissus (UTCT), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

8. Pediatric acute graft-versus-host disease prophylaxis and treatment: surveyed real-life approach reveals dissimilarities compared to published recommendations Correspondence Transplant International

Author

Lawitschka, Anita, Lucchini, Giovanna, Strahm, Brigitte, Dalle, Jean-Hugues, Gibson, Brenda, Balduzzi, Adriana, Diaz De Heredia, Cristina, Wachowiak, Jacek, Dalissier, Arnaud, Vettenranta, Kim, Yaniv, Isaac, Bordon, Victoria, Bauer, Dorothea, Bader, Peter, Meisel, Roland, Peters, Christina, Corbacioglu, Selim, Medizinische Universität Wien = Medical University of Vienna, Great Ormond Street Hospital for Children [London] (GOSH), University of Freiburg [Freiburg], Hôpital Robert Debré Paris, Hôpital Robert Debré, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Vall d'Hebron University Hospital [Barcelona], Poznan University of Medical Sciences [Poland] (PUMS), 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), University of Helsinki, Tel Aviv University [Tel Aviv], Ghent University Hospital, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], and Universität Regensburg (UR)

Subjects
acute GVHD, surgical procedures, operative, pediatrics, treatment, immune system diseases, hemic and lymphatic diseases, [SDV]Life Sciences [q-bio], hematopoietic cell transplantation, prophylaxis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Pediatric allogeneic hematopoietic cell transplantation (HCT) practices differ from those of adults, particularly the heterogeneity of transplantable nonmalignant diseases and the lower incidence of graft-versus-host disease (GVHD). Several guidelines regarding the management of acute (a) GVHD in adult HCT have been published. We aimed to capture the real-life approaches for pediatric aGVHD prophylaxis/treatment, and data from 75/193 (response rate 39%) EBMT centers (26 countries) were included, representing half (48%) of the pediatric EBMT-HCT activity. Results with ≥75% approval from respondents (74/75) for GVHD prophylaxis after myeloablative HCT for malignancies partially contradict published guidelines: Single-agent cyclosporine A (CsA) was used for matched sibling donor HCT in 47%; blood CsA levels were reported lower; the relapse risk in malignant diseases influenced GVHD prophylaxis with early withdrawal of CsA; distinct longer duration of CsA was employed in nonmalignant diseases. Most centers used additional anti-thymocyte globulin for matched unrelated and mismatched donor HCT, but not for matched siblings. Regarding prophylaxis in nonmyeloablative conditioning (mainly for nonmalignant diseases), responses showed broad heterogeneity. High conformity was found for first-line treatment; however, results regarding steroid-refractory aGVHD indicate an earlier diagnosis in children. Our findings highlight the need for standardized pediatric approaches toward aGVHD prophylaxis/treatment differentiated for malignant and nonmalignant underlying diseases.

Published
2020

9. Correction: Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Nava, Tiago, Ansari, Marc, Dalle, Jean-Hugues, de Heredia, Christina Diaz, Güngör, Tayfun, et al, and University of Zurich

Subjects
10036 Medical Clinic, 2747 Transplantation, 2720 Hematology, 610 Medicine & health
Published
2020

10. Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Nava, Tiago, Ansari, Marc, Dalle, Jean-Hugues, de Heredia, Christina Diaz, Güngör, Tayfun, et al, and University of Zurich

Subjects
10036 Medical Clinic, 2747 Transplantation, 2720 Hematology, 610 Medicine & health
Published
2020

12. Risk factors and outcomes according to age at transplantation with an HLA-identical sibling for sickle cell disease

Author

Cappelli, Barbara, Volt, Fernanda, Tozatto-Maio, Karina, Scigliuolo, Graziana Maria, Ferster, Alina, Dupont, Sophie, Simões, Belinda Pinto, Al-Seraihy, Amal, Aljurf, Mahmoud D, Almohareb, Fahad, Belendez, Cristina, Matthes, Susanne, Dhedin, Nathalie, Pondarre, Corinne, Dalle, Jean-Hugues, Bertrand, Yves, Vannier, Jean Pierre, Kuentz, Mathieu, Lutz, Patrick, Michel, Gérard, Rafii, Hanadi, Neven, Benedicte, Zecca, Marco, Bader, Peter, Cavazzana, Marina, Labopin, Myriam, Locatelli, Franco, Magnani, Alessandra, Ruggeri, Annalisa, Rocha, Vanderson, Bernaudin, Françoise, de La Fuente, Josu, Corbacioglu, Selim, Gluckman, Eliane, Eurocord, The Cellular Therapy and Immunobiology Working Party (CTIWP), The Paediatric Diseases Working Party (PDWP) of the EBMT, and UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Anemia, Graft vs Host Disease, Disease, Human leukocyte antigen, Anemia, Sickle Cell, Young Adult, HLA Antigens, hemic and lymphatic diseases, Medicine, Humans, Sibling, Young adult, Child, Online Only Articles, Survival rate, business.industry, Incidence (epidemiology), Histocompatibility Testing, Incidence, Age Factors, Hematopoietic Stem Cell Transplantation, Infant, Généralités, thalassemia, children, adults, Hematology, medicine.disease, Prognosis, Transplantation, Europe, Survival Rate, surgical procedures, operative, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Child, Preschool, HSCT, Female, business, Follow-Up Studies
Abstract

SCOPUS: le.j, info:eu-repo/semantics/published

Published
2019

13. Single-Unit versus Double-Unit Umbilical Cord Blood Transplantation in Children and Young Adults with Residual Leukemic Disease

Author

Bensussan, Armand, Janela, Baptiste, Thonnart, Nicolas, Bagot, Martine, Musette, Philippe, Ginhoux, Florent, Marie-Cardine, Anne, Balligand, Laura, Galambrun, Claire, Sirvent, Anne, Roux, Clémence, Pochon, Cécile, Bruno, Bénédicte, Jubert, Charlotte, Loundou, Anderson, Esmiol, Sophie, Yakoub-Agha, Ibrahim, Forcade, Edouard, Paillard, Catherine, Marie-Cardine, Aude, Plantaz, Dominique, Gandemer, Virginie, Blaise, Didier, Rialland, Fanny, Renard, Cecile, Seux, Mylène, Baumstarck, Karine, Mohty, Mohamad, Dalle, Jean-Hugues, Michel, Gérard, CCSD, Accord Elsevier, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Jeanne de Flandre [Lille], Université de Lille, CHU Bordeaux [Bordeaux], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), CHU Marseille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Strasbourg, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pontchaillou [Rennes], 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Assistance Publique - Hôpitaux de Marseille (APHM), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré, Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Dermatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de médecine (AMU MED), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Pasteur [Nice] (CHU), Institut d'Histoire de la Pensée Classique (IHPC), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Service Hématologie Infantile, CHU Grenoble, Hématogoie pédiatrique, hôpital Sud, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Cryopic, Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Sud, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Cord blood unit, Disease, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Prospective Studies, Young adult, Children, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Transplantation, Acute leukemia, business.industry, Minimal residual disease, Stem cell transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 3. Good health, body regions, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Double-Unit Umbilical Cord Blood Transplantation, Cord blood, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cord Blood Stem Cell Transplantation, business, 030215 immunology, Young adults
Abstract

International audience; We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single- versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of ≥10-4, which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 ± 4.4%, and it was not significantly influenced by the MRD level: 70.7 ± 5.4% in MRD-negative (

Published
2019

14. Efficacy and safety of defibrotide in the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome following hematopoietic stem cell transplantation: Interim results from the defifrance study

Author

Mohty, Mohamad, Labopin, Myriam, Lebon, Delphine, Berceanu, Ana, Jubert, Charlotte, Yakoub-Agha, Ibrahim, Girault, Stephane, Detrait, Marie, Pochon, Cecile, Rialland, Fanny, Gandemer, Virginie, Latour, Regis Peffault, David Michonneau, Delaval, Floriane, Michel, Gerard, Sirvent, Anne, Clement, Laurence, Menard, Anne-Lise, Huynh, Anne, Bouvatier, Virginie, Hanvesakul, Raj, Medeghri, Zakaria, Dalle, Jean-Hugues, 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), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Limoges, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and DESSAIVRE, Louise

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

45th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Frankfurt, GERMANY, MAR 24-27, 2019; International audience

Published
2019

15. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation

Author

Groll, Andreas H, Castagnola, Elio, Cesaro, Simone, Dalle, Jean Hugues, Engelhard, Dan, Hope, William, Roilides, Emmanuel, Styczynski, Jan, Warris, Adilia, Lehrnbecher, Thomas, Leukaemia, on behalf of the Fourth European Conference on Infections in, joint venture of the Infectious Diseases Working Party of the European Group for Blood, Marrow Transplantation, A, Cancer, the Infectious Diseases Group of the European Organisation for Research, Treatment, Of, Society, the International Immunocompromised Host, and Net, the European Leukaemia

Subjects
pediatric, hematopoietic stem cell transplantation, guidelines, invasive fungal infection, Hematologic Diseases
Published
2014

16. The impact of donor type on the outcome of pediatric patients with very high risk acute lymphoblastic leukemia

Author

Taifun Gungor, Marc Bierings, Jean Hugues Dalle, Marianne Ifversen, Ulrike Poetschger, Christina Peters, Petr Sedlacek, Isaac Yaniv, Adriana Balduzzi, Anna Pieczonka, Arjan C. Lankester, Evgenia Glogova, Jacek Wachowiak, Peter Bader, Peter Svec, Akif Yeşilipek, Jacek Toporski, Dalle, J, Balduzzi, A, Bader, P, Pieczonka, A, Yaniv, I, Lankester, A, Bierings, M, Yesilipek, A, Sedlacek, P, Ifversen, M, Svec, P, Toporski, J, Gungor, T, Wachowiak, J, Glogova, E, Poetschger, U, Peters, C, University of Zurich, and Dalle, Jean-Hugues

Subjects
Oncology, medicine.medical_specialty, Transplantation Conditioning, 2747 Transplantation, medicine.medical_treatment, 2720 Hematology, Graft vs Host Disease, 610 Medicine & health, Hematopoietic stem cell transplantation, Article, 03 medical and health sciences, 0302 clinical medicine, Median follow-up, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Child, Kaplan–Meier estimator, Retrospective Studies, Transplantation, Chemotherapy, Acute lymphocytic leukaemia, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Tissue Donors, Treatment Outcome, Risk factors, 10036 Medical Clinic, 030220 oncology & carcinogenesis, Child, Preschool, Cohort, business, Ex vivo, acute lymphoblastic leukemia, hematopoietic stem cell transplantation, mismatched donor, 030215 immunology
Abstract

Allogeneic HSCT represents the only potentially curative treatment for very high risk (VHR) ALL. Two consecutive international prospective studies, ALL-SCT-(I)BFM 2003 and 2007 were conducted in 1150 pediatric patients. 569 presented with VHR disease leading to any kind of HSCT. All patients >2 year old were transplanted after TBI-based MAC. The median follow-up was 5 years. 463 patients were transplanted from matched donor (MD) and 106 from mismatched donor (MMD). 214 were in CR1. Stem cell source was unmanipulated BM for 330 patients, unmanipulated PBSC for 135, ex vivo T-cell depleted PBSC for 62 and cord-blood for 26. There were more advanced disease, more ex vivo T-cell depletion, and more chemotherapy based conditioning regimen for patients transplanted from MMD as compared to those transplanted from MSD or MD. Median follow up (reversed Kaplan Meier estimator) was 4.99 years, median follow up of survivals was 4.88, range (0.01–11.72) years. The 4-year CI of extensive cGvHD was 13 ± 2% and 17 ± 4% (p = NS) for the patients transplanted from MD and MMD, respectively. 4-year EFS was statistically better for patients transplanted from MD (60 ± 2% vs. 42 ± 5%, p p

Published
2020

17. Ontogeny of human mucosal-associated invariant T cells and related T cell subsets

Author

Jean-Sébastien Diana, Michel Peuchmaur, Jean-Hugues Dalle, Valérie Biran, Saba Azarnoush, Marie Tourret, Véronique Houdouin, Liana Ghazarian, Thomas Schmitz, Ghada Ben Youssef, Yvonne K. Mburu, Marion Lambert, Olivier Lantz, Sophie Caillat-Zucman, Marion Salou, Anne-Laure Virlouvet, Stanislas Mondot, Ben Youssef, Ghada, Tourret, Marie, Salou, Marion, Ghazarian, Liana, Dalle, Jean-Hugues, Lantz, Olivier, Biran, Valérie, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Département de Biopathologie, Hôpital Saint-Louis, Agence Nationale de la Recherche (ANR), Direction Generale de l'Offre de Soins (DGOS) PRTS 14-CE15-0005, Institut National du Cancer (INCa) 2012-059, Agence de Biomedecine, Cent pour Sang la vie, IRG HET, Fondation pour la Recherche Medicale (FRM) ING20150532367, Agence Nationale de la Recherche grants from the 'Investissements d'Avenir' program ANR-10-EQPX-03 ANR-10-INBS-09-08, Canceropole Ile-de-France, and SiRIC-Curie program INCa-DGOS-4654

Subjects
0301 basic medicine, Adult, Male, Ontogeny, T cell, [SDV]Life Sciences [q-bio], Immunology, Receptors, Antigen, T-Cell, Mucosal associated invariant T cell, Biology, Infections, Mucosal-Associated Invariant T Cells, Article, Minor Histocompatibility Antigens, 03 medical and health sciences, 0302 clinical medicine, Antigen, Pregnancy, T-Lymphocyte Subsets, medicine, Immunology and Allergy, Humans, Cord blood transplantation, Research Articles, Antigens, Bacterial, Histocompatibility Antigens Class I, MAIT Cells, Infant, Newborn, Cell Differentiation, Fetal Blood, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Cord blood, Female, 030215 immunology, NK Cell Lectin-Like Receptor Subfamily B
Abstract

There are very few human MAIT cells in cord blood. Ben Youssef et al. show that they slowly expand during childhood and point to a critical role of the TCRαβ repertoire in determining their unique ability to recognize MR1-restricted microbial antigens., Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2+ CD161highCD4− T cells that recognize microbial riboflavin precursor derivatives such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood, but there are very few in cord blood. We longitudinally studied Vα7.2+ CD161high T cell and related subset levels in infancy and after cord blood transplantation. We show that Vα7.2+ and Vα7.2− CD161high T cells are generated early during gestation and likely share a common prenatal developmental program. Among cord blood Vα7.2+ CD161high T cells, the minority recognizing MR1:5-OP-RU display a TRAV/TRBV repertoire very similar to adult MAIT cells. Within a few weeks of life, only the MR1:5-OP-RU reactive Vα7.2+ CD161high T cells acquire a memory phenotype. Only these cells expand to form the adult MAIT pool, diluting out other Vα7.2+ CD161high and Vα7.2− CD161high populations, in a process requiring at least 6 years to reach adult levels. Thus, the high clonal size of adult MAIT cells is antigen-driven and likely due to the fine specificity of the TCRαβ chains recognizing MR1-restricted microbial antigens.

Published
2017

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