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1. Correction: Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients

Author

Florent Malard, Christoph Schmid, Ali Bazarbachi, Gesine Bug, Dietrich W. Beelen, Uwe Platzbecker, Norbert Claude Gorin, Anne Huynh, Noel Milpied, Roni Shouval, Jan J. Cornelissen, Charles Craddock, Arnon Nagler, Myriam Labopin, Maria H. Gilleece, Riitta Niittyvuopio, Francesco Lanza, Eolia Brissot, Mohamad Mohty, Sebastian Giebel, Jordi Esteve, Alexandros Spyridonidis, Mahmoud Aljurf, J. Sanz, Didier Blaise, Arnold Ganser, Annalisa Ruggeri, Zinaida Peric, Jurjen Versluis, Bipin N. Savani, Fabio Ciceri, Yngvar Fløisand, Frédéric Baron, Laimonas Griskevicius, Gérard Socié, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Transplantation, Pediatrics, medicine.medical_specialty, Transplant Conditioning, Bone marrow transplantation, business.industry, Medizin, Myeloid leukemia, Hematology, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract

In the original publication, the author Mahmoud Aljurf was omitted from the author list. This author’s affiliation is 'Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia'. This has been corrected in both the PDF and HTML versions of the original article.

Published
2020
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2. Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies

Author

Giorgia Battipaglia, Marie-Thérèse Rubio, Eolia Brissot, Myriam Labopin, Tounes Ledraa, Remy Dulery, Françoise Isnard, Anne Vekhoff, Juliana Bastos, Ollivier Legrand, Mohamad Mohty, Simona Sestili, Federica Giannotti, Zinaida Peric, Ramdane Belhocine, Razan Mohty, Annalisa Ruggeri, Simona Lapusan, Clemence Mediavilla, Agnès Bonnin, Florent Malard, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Peric, Z., Mohty, R., Bastos, J., Brissot, E., Battipaglia, G., Belhocine, R., Sestili, S., Giannotti, F., Vekhoff, A., Ledraa, T., Legrand, O., Lapusan, S., Isnard, F., Labopin, M., Bonnin, A., Mediavilla, C., Rubio, M. -T., Ruggeri, A., Dulery, R., Malard, F., and Mohty, M.

Subjects
medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, ThioTEPA, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Refractory, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Antilymphocyte Serum, Transplantation, Neutrophil Engraftment, Hematologic Neoplasms / therapy, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Regimen, surgical procedures, operative, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Transplantation, Haploidentical, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, Neoplasm Recurrence, Local, business, Graft vs Host Disease / prevention & control, Thiotepa, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract

We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa-busulfan-fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa-etoposide-cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17-72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180-1595) days. The median days to neutrophil engraftment was 17 (range, 12-34). The cumulative incidences (CI) of acute graft-versus-host disease (GVHD) grade III to IV, severe chronic GVHD, nonrelapse mortality (NRM), and relapse were 16%, 16%, 26, and 26%, respectively. The 2-year overall survival (OS) and disease-free survival (DFS) were 53% and 47%, respectively. There were no significant differences between the patients in CR and R/R patients in terms of engraftment, GVHD, NRM, relapse, OS, or DFS. We conclude that thiotepa-based regimen with PT-CY can be modified with PBSC and ATG, still providing low toxicity, protection against GVHD, and low relapse incidence. Particularly encouraging are the results with the modification to sequential regimen in R/R patients.

Published
2020
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3. Hematopoietic stem cell transplantation for patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a retrospective study of 21 patients from SFGM-TC centers

Author

Alban Villate, Marie-Thérèse Rubio, Patrice Chevallier, Ibrahim Yakoub-Agha, Reza Tabrizi, Pierre-Simon Rohrlich, Nicolas Vallet, Louis Terriou, Jonathan Farhi, Deborah Desmier, Fiorenza Barraco, Raynier Devillier, Natacha Maillard, Mohamad Mohty, Régis Peffault de Latour, Annalisa Ruggeri, Patrice Ceballos, Steéphanie Nguyen, Gaelle Guillerm, Flore Sicre de Fontbrune, Michael Loschi, Xavier Poiré, Gérard Socié, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service Hématologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Hôpital l'Archet, Hôpital Lapeyronie [Montpellier] (CHU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, Hemoglobinuria, Paroxysmal, CD59, Hematopoietic stem cell transplantation, Antibodies, Monoclonal, Humanized, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Registries, Online Only Articles, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, Hematopoietic stem cell, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Eculizumab, medicine.disease, Hemolysis, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Monoclonal, Paroxysmal nocturnal hemoglobinuria, Hemoglobinuria, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder which manifests with hemolysis (classical PNH) due to loss of expression of the CD55 and CD59 proteins, which leads to complement mediated cell lysis.[1][1] Despite being the only curative treatment for PNH

Published
2018
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4. Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia: a nationwide phase 2 study

Author

Catherine Paillard, Mohamad Mohty, Claire Galambrun, Charlotte Jubert, Gérard Socié, Fanny Rialland, Eliane Gluckman, Jérôme Larghero, S. Furst, Annalisa Ruggeri, Marie-Thérèse Rubio, Virginie Gandemer, Jacques-Olivier Bay, Jean-Hugues Dalle, Sylvie Chevret, Flore Sicre de Fontbrune, Régis Peffault de Latour, Bénédicte Bruno, Anne Sirvent, Edouard Forcade, Jérôme Cornillon, Pierre S. Rorlich, Alexandra Salmon, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Adolescent, Anemia, Immunology, Graft vs Host Disease, Cord Blood Stem Cell Transplantation, Biochemistry, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Aplastic anemia, Child, Survival rate, ComputingMilieux_MISCELLANEOUS, Antilymphocyte Serum, Alanine, business.industry, Umbilical Cord Blood Transplantation, Anemia, Aplastic, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Total body irradiation, Allografts, medicine.disease, 3. Good health, Survival Rate, Transplantation, 030220 oncology & carcinogenesis, Acute Disease, Female, Unrelated Donors, business, Whole-Body Irradiation, 030215 immunology
Abstract

Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.

Published
2018
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5. Unmanipulated haploidentical stem cell transplantation in adults with acute lymphoblastic leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

Author

Johanna Tischer, Arnon Nagler, Yener Koc, Sebastian Giebel, Annalisa Ruggeri, William Arcese, Boris V. Afanasyev, Myriam Labopin, He Huang, Nicole Santoro, Mohamad Mohty, Andrea Bacigalupo, Depei Wu, Stella Santarone, Zafer Gulbas, Fabio Ciceri, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Medicine, Division of Hematology and Clinical Immunology [Perugia, Italy], Università degli Studi di Perugia (UNIPG), Department of Hematology II [Genova, Italy], Ospedale San Martino [Genova, Italy], Università cattolica del Sacro Cuore [Roma] (Unicatt), Hematology and Bone Marrow Transplantation Unit [Milan, Italy], IRCCS Ospedale San Raffaele [Milan, Italy], Hematology Department [Kocaeli, Turkey], Anadolu Medical Center [Kocaeli, Turkey], Bone Marrow Transplantation Center [Zhejiang, China], The First Affiliated Hospital of Zhengzhou University-Zhejiang University School of Medicine [China], Hematology and Transplantology [St. Petersburg, Russian Federation], First Pavlov State Medical University of St. Petersburg [Russian Federation]-Ratsa Gorbacheva Memorial Children's Institute [St. Petersburg, Russian Federation], Department of Hematology [Rome, Italy], Stem Cell Transplant Unit [Rome, Italy], Università degli Studi di Roma Tor Vergata [Roma]-Università degli Studi di Roma Tor Vergata [Roma], Department of Hematology [Jiangsu, China], The First Affiliated Hospital of Soochow University [Suzhou, China], Stem Cell Transplant Unit [Antalya, Turkey], Medical Park Antalya Hospital [Turkey], Department of Internal Medicine III [Munich, Germany], Hematopoietic Stem Cell Transplantation [Munich, Germany], Ludwig Maximilian University [Munich] (LMU)-Ludwig Maximilian University [Munich] (LMU), Department of Hematology and Trasfusional Medicine [Pescara, Italy], Ospedale Civile - BMT Center [Pescara, Italy], Department of Bone Marrow Transplantation and Onco-Hematology [Gliwice, Poland], Center of Oncology - Maria Sklodowska-Curie Memorial Institute, Branch in Gliwice [Poland], Department of Hematology and Bone Marrow Transplantation [Ramat Gan, Israel], Chaim Sheba Medical Center [Ramat Gan, Israel], Santoro, Nicole, Ruggeri, Annalisa, Labopin, Myriam, Bacigalupo, Andrea, Ciceri, Fabio, Gã¼lbaå , Zafer, Huang, He, Afanasyev, Bori, Arcese, William, Wu, Depei, Koc, Yener, Tischer, Johanna, Santarone, Stella, Giebel, Sebastian, Mohty, Mohamad, Nagler, Arnon, BMC, BMC, Università degli Studi di Perugia = University of Perugia (UNIPG), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), and Ratsa Gorbacheva Memorial Children's Institute [St. Petersburg, Russian Federation]-First Pavlov State Medical University of St. Petersburg [Russian Federation]

Subjects
Oncology, Male, Cancer Research, Transplantation Conditioning, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Hematopoietic stem cell transplantation, Acute lymphoblastic leukemia, 0302 clinical medicine, hemic and lymphatic diseases, Cumulative incidence, Non-TCD haploidentical, Acute leukemia, Hematology, Hematopoietic Stem Cell Transplantation, lcsh:Diseases of the blood and blood-forming organs, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, surgical procedures, operative, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Allogenic stem cell transplantation, Cyclophosphamide, Adolescent, lcsh:RC254-282, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Transplantation, Homologous, Adults, Molecular Biology, Aged, Retrospective Studies, business.industry, lcsh:RC633-647.5, Research, Survival Analysis, Transplantation, Regimen, Bone marrow, Neoplasm Recurrence, Local, business, 030215 immunology
Abstract

Background Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors. Methods We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014. Results Median age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on anti-thymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II–IV acute-graft-versus-host-disease (GVHD) was 31%, grade III–IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS. Conclusions Unmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status. Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0480-5) contains supplementary material, which is available to authorized users.

Published
2016
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6. Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study

Author

Matthias Stelljes, Myriam Labopin, Gerhard Ehninger, Johanna Tischer, Pavel Jindra, Nicolaus Kröger, Arnold Ganser, Annalisa Ruggeri, Dietrich W. Beelen, Arnon Nagler, Bertram Glass, Mohamad Mohty, Rainer Schwerdtfeger, Mauricette Michallet, Giorgia Battipaglia, Renate Arnold, Jürgen Finke, 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), Università degli studi di Napoli Federico II, Technische Universität Dresden = Dresden University of Technology (TU Dresden), University Hospital Essen, Ludwig-Maximilians University [Munich] (LMU), Hannover Medical School [Hannover] (MHH), Helios-Klinikum Berlin-Buch, Asklepios Klinik St. Georg Hamburg, University Medical Centre Freiburg, Hematology Laboratory, Hospices Civils de Lyon, Westfälische Wilhelms-Universität Münster (WWU), Charles University Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Chaim Sheba Medical Center, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, University of Naples Federico II = Università degli studi di Napoli Federico II, Ludwig-Maximilians-Universität München (LMU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Ruggeri, A., Battipaglia, G., Labopin, M., Ehninger, G., Beelen, D., Tischer, J., Ganser, A., Schwerdtfeger, R., Glass, B., Finke, J., Michallet, M., Stelljes, M., Jindra, P., Arnold, R., Kroger, N., Mohty, M., and Nagler, A.

Subjects
Male, Registrie, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, Medizin, Graft vs Host Disease, Blood Donors, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, Gastroenterology, 0302 clinical medicine, Recurrence, Retrospective Studie, Cumulative incidence, Registries, Relapse, Hematology, Incidence (epidemiology), Graft Survival, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Survival Rate, Leukemia, Myeloid, Acute, Oncology, 030220 oncology & carcinogenesis, Female, Unrelated Donors, Human, Adult, medicine.medical_specialty, Unrelated donor, Sibling, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Disease-Free Survival, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Unrelated Donor, Internal medicine, medicine, Humans, Molecular Biology, Retrospective Studies, Aged, Matched sibling donor, Neutrophil Engraftment, Acute myeloid leukemia, business.industry, lcsh:RC633-647.5, Research, Siblings, Surgery, Transplantation, business, 030215 immunology
Abstract

International audience; Background: Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated.Methods: We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3–157) months.Results: Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II–IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p

Published
2016
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7. Impact of HLA of Winning Cord Blood Unit on Outcomes after Double Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: A Retrospective Study on Behalf of Eurocord, the Cord Blood Committee Cellular Therapy and Immunobiology Working Party and the Acute Leukemia Working Party of the EBMT

Author

Nigel H. Russell, Eliane Gluckman, Dimitrios Karakasis, Annalisa Ruggeri, Gérard Socié, Eric Deconinck, Pierre-Simon Rohrlich, Mauricette Michallet, Pierre Feugier, Henrik Sengeloev, Thierry Lamy, Vanderson Rocha, Jan J. Cornelissen, Arnon Nagler, Noel-Jean Milpied, Myriam Labopin, Eefke Petersen, Charles Craddock, Didier Blaise, Federica Giannotti, Mohamad Mohty, Chantal Kenzey, 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), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre International des greffes [CHU Saint-Antoine] (EBMT), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Service de pédiatrie, 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], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Relations Hôte-Environnement (RHEM), Université Henri Poincaré - Nancy 1 (UHP), CHU Pontchaillou [Rennes], Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), France Monacord, Centre Scientifique de Monaco (CSM), Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center at Tel hashomer, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
medicine.medical_specialty, Acute leukemia, Thymoglobulin, Umbilical Cord Blood Transplantation, business.industry, [SDV]Life Sciences [q-bio], Immunology, Retrospective cohort study, Cell Biology, Hematology, Human leukocyte antigen, medicine.disease, Biochemistry, 3. Good health, Transplantation, Leukemia, Internal medicine, Cord blood, medicine, Intensive care medicine, business
Abstract

Umbilical cord blood transplantation (UCBT) from unrelated donor is a valid alternative for patients (pts) with acute leukemia (AL) who lack an HLA matched donor. Double UCBT (dUCBT) has extended the use of UCBT to adults. In the majority of the cases, chimerism analysis shows that one unit emerges as the sole source of long term hematopoiesis in the recipient (rcp) following dUCBT. However, no clear factor has yet been identified to reliably predict which unit will emerge as the predominant one. With the aim of analyzing factors that may predict cord blood unit (CBU) predominance and the impact of the winning CBU characteristics on outcomes after dUCBT, we studied adults with AL who underwent dUCBT as first transplant between 2004 and 2013 at EBMT centres. We selected pts who achieved engraftment and who had available chimerism data assessed within day 130 after dUCBT, with one of the CBUs representing at least 50% of the rcp hematopoiesis (winCBU). According to these criteria, 347 pts were included: 323 had full donor (18 being dual chimera) and 24 had mixed chimerism (>5% of donor cells). At diagnosis, 35% had ALL and 65% AML. At dUCBT 45% were in first complete remission (CR), 44% in second CR and 11% had more advanced disease. Overall, 33% had high risk cytogenetic features. Median time from diagnosis to dUCBT was 12 months (range, 2-202), median age was 40 years (y) (18-76). Conditioning regimen (CT) was reduced intensity (RIC) in 52%. Cyclophosphamide+fludarabine+total body irradiation was the most frequent CT (63%). Anti-thymoglobulin (ATG) was administrated in 25% of the transplants. Median number of total nucleated cells (TNC) and CD34+ cells at cryopreservation were 5.1x107/Kg (range, 2.3-13.7) and 1.3x105/Kg (range, 0.4-10.7), respectively. Considering the unit with the highest number of HLA mismatches (MMs) with the rcp, 73% of the donors were matched at 4 or less loci (≤4/6). For winCBUs, median number of TNC and CD34 cells at cryopreservation were 2.5x107/Kg (range, 0.95-6) and 1x105/Kg (range, 0.06-10), respectively. Only 4% of the winCBUs were 6/6 HLA-matched to the rcp, while 37% were 5/6, 55% were 4/6 and 4% were 3/6 HLA-matched. Overall, 54% of the winCBUs were gender matched and 38% were ABO compatible with the rcp. WinCBUs median age was 3.4 years (range, 0.2-14). As for inter unit characteristics, 50% of the pts received gender matched units. Units were ABO compatible in 40% of the cases, while 30% had minor and 30% had major ABO incompatibility. In our study population, median follow-up for survivors was 35 months (range, 3-99). All pts engrafted with neutrophil >0.5x109/L in a median time of 25 days (range, 6-66) post DCBT. No secondary graft failure was reported. The cumulative incidence (CI) of acute GvHD grade II-IV at 100 days was 41% with a median time of onset of 29 days (range, 7-106). The 3y-CI of chronic GvHD was 41% (50% of the pts had extensive). The 3y-CI of relapse (RI) and transplant related mortality (TRM) were 27% and 24%, respectively. At 3y, leukemia free survival (LFS) was 49% and overall survival (OS) was 54%. In multivariate analysis (MVA) including unit characteristics (HLA and gender matching, type of HLA MMs, number of TNC and CD34 cells at cryopreservation, ABO compatibility and unit age) and inter unit features (gender match, ABO compatibility), no significant factor predicting the winCBU was identified. Analyzing the impact of winCBU on dUCBT outcomes, the HLA matching between CBU and the rcp was the only characteristic related to the winCBU significantly affecting results. The 3y-LFS for pts with 6/6 or 5/6 HLA-matched winCBUs was 56% as compared to 44% for those with 4/6 (p=0.03), while OS was 62% versus 49% (p=0.01), respectively. Acute GvHD was increased in pts receiving a 4/6 HLA-matched winCBU (46% versus 35% for those 6/6 or 5/6, p=0.04). In MVA, 4/6 HLA-matched winCBU was associated with decreased LFS (HR 1.5, p=0.03) and OS (HR 1.5, p=0.03), and with increased TRM (HR 1.9, p=0.03) and acute GvHD (HR 1.7, p=0.01). Notably, older winCBUs (>3.4y) were associated with higher acute GvHD (48% versus 35%; HR 1.6, p=0.02). Other factors associated with poor outcomes were advanced disease status and the use of ATG. Although we failed to identified any factor predicting CBU predominance, we were able to demonstrate that a 4/6 HLA matched winCBU is associated with poor outcomes. Therefore, selecting units with lower number of HLA MMs for dUCBT may improve final outcomes. Disclosures Russell: Therakos: Other: shares. Mohty:Riemser: Honoraria, Research Funding. Nagler:Biokine LTD: Consultancy.

Published
2015
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8. Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Author

Eliane Gluckman, Tracey A. O'Brien, Cristina Navarrete, Maria Pia Sormani, Mary Eapen, Gesine Kögler, Myriam Labopin, Juliana Ruiz Fernandes, Anna Paola Iori, Federico Garnier, Jaime Sanz, Fernanda Volt, Guillermo Sanz, Lucilla Lecchi, Chantal Kenzey, Riccardo Saccardi, Fabienne Pouthier, Cristina Díaz de Heredia, Franco Locatelli, Sergi Querol, Vanderson Rocha, Etienne Baudoux, Annalisa Ruggeri, Gérard Michel, William Arcese, 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), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cord blood committee EBMT, Università degli studi di Genova = University of Genoa (UniGe), Hospital La Fe, Hôpital de la Timone [CHU - APHM] (TIMONE), Santa Lucia Foundation, IRCSS, Rome, Vall d'Hebron University Hospital [Barcelona], Sydney Children's hospital, Rome transplant network, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Barcelona Cord Blood Bank, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Maggiore Hospital, IRCCS Foundation, Milano, Etablissement français du sang [Besançon] (EFS), Agence de la biomédecine [Saint-Denis la Plaine], NHSBT, Université de Liège, Medical College of Wisconsin, France Monacord, Centre Scientifique de Monaco (CSM), Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Careggi University Hospital, HAL UPMC, Gestionnaire, 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), Universita degli studi di Genova, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], and Dusseldorf University

Subjects
Graft Rejection, Myeloid, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Time Factors, Transplantation Conditioning, Neutrophils, Graft vs Host Disease, Umbilical cord, 0302 clinical medicine, Cumulative incidence, Child, Adolescent, Adult, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Leukemia, Myeloid, Acute, Middle Aged, Myeloablative Agonists, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Remission Induction, Survival Analysis, Transplantation, Homologous, Cord Blood Stem Cell Transplantation, Acute leukemia, Leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Hematology, 3. Good health, medicine.anatomical_structure, surgical procedures, operative, N/A, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, 030220 oncology & carcinogenesis, Homologous, medicine.medical_specialty, Acute, 03 medical and health sciences, medicine, Preschool, Transplantation, Neutrophil Engraftment, business.industry, Umbilical Cord Blood Transplantation, Settore MED/15, Surgery, business, 030215 immunology
Abstract

on behalf of Eurocord, Cord Blood Committee EBMT and Netcord; International audience; Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.

Published
2014
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9. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France

Author

Eliane Gluckman, Vanderson Rocha, Mauricette Michallet, Norbert Claude Gorin, Catherine Faucher, Didier Blaise, Gérard Socié, Nathalie Fegueux, Myriam Labopin, Jean-Yves Cahn, Stéphanie Nguyen, Eric Deconinck, Federico Garnier, Dominique Bertrand, Thierry de Revel, Fernanda Volt, Chantal Kenzey, Namik Taright, Noel Milpied, Lionel Mannone, Mohamad Mohty, Ibrahim Yakoub Agha, Annalisa Ruggeri, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Università degli Studi di Roma Tor Vergata [Roma], 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], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital l'Archet, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital JeanMinjoz, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Michallon, Hôpital d'Instruction des Armées Percy, Service de Santé des Armées, Agence de la biomédecine [Saint-Denis la Plaine], DIM Paris, Centre national gestion Paris, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, HAL UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Saint-Antoine [AP-HP]

Subjects
Adult, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, Cord, Adolescent, Cost effectiveness, Cost-Benefit Analysis, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cord Blood Stem Cell Transplantation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Recurrence, Risk Factors, medicine, Humans, Transplantation, Homologous, Aged, Acute leukemia, Leukemia, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, 3. Good health, Surgery, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Cord blood, Acute Disease, France, business, 030215 immunology
Abstract

on behalf of Eurocord and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC); International audience; Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years.

Published
2014
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