Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC

Abstract Background Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell...

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Main Authors: Florent Malard, Myriam Labopin, Christina Cho, Didier Blaise, Esperanza B. Papadopoulos, Jakob Passweg, Richard O’Reilly, Edouard Forcade, Molly Maloy, Liisa Volin, Hugo Castro-Malaspina, Yosr Hicheri, Ann A. Jakubowski, Corentin Orvain, Sergio Giralt, Mohamad Mohty, Arnon Nagler, Miguel-Angel Perales
Format: Article
Language:English
Published: BMC 2018-10-01
Series:Journal of Hematology & Oncology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13045-018-0668-3
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spelling doaj-db7a0aa4e22246feb663ac34dbbbbb582020-11-25T01:15:36ZengBMCJournal of Hematology & Oncology1756-87222018-10-0111111110.1186/s13045-018-0668-3Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCCFlorent Malard0Myriam Labopin1Christina Cho2Didier Blaise3Esperanza B. Papadopoulos4Jakob Passweg5Richard O’Reilly6Edouard Forcade7Molly Maloy8Liisa Volin9Hugo Castro-Malaspina10Yosr Hicheri11Ann A. Jakubowski12Corentin Orvain13Sergio Giralt14Mohamad Mohty15Arnon Nagler16Miguel-Angel Perales17Service d’Hématologie Clinique et Thérapie Cellulaire, AP-HP, Hôpital Saint-AntoineService d’Hématologie Clinique et Thérapie Cellulaire, AP-HP, Hôpital Saint-AntoineAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer CenterProgramme de Transplantation & Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli CalmettesAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer CenterUniversity Hospital, HematologyBone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer CenterCHU Bordeaux, Hôpital Haut-levequeAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer CenterStem Cell Transplantation Unit, HUCH Comprehensive Cancer CenterAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer CenterDépartement d’Hématologie Clinique, CHU LapeyronieAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer CenterService des Maladies du Sang, CHRUAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer CenterService d’Hématologie Clinique et Thérapie Cellulaire, AP-HP, Hôpital Saint-AntoineEBMT Paris Study Office/CEREST-TCAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer CenterAbstract Background Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors. Results Two-year overall survival estimate was 69.9% (95% CI, 58.5–69.4) in the ATG group and 67.6% (95% CI, 60.3–74.9) in the CD34+ group (p = 0.31). The cumulative incidence of grade II–IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1–3.7), p = 0.02; HR 15.1 (95% CI 5.3–42.2), p < 0.0001]. Parameters associated with a lower GVHD-free relapse-free survival (GRFS) were ATG [HR 1.6 (95% CI 1.1–2.2), p = 0.006], adverse cytogenetic [HR 1.7 (95% CI 1.3–2.2), p = 0.0004], and the use of an unrelated donor [HR 1.4 (95% CI 1.0–1.9), p = 0.02]. There were no statistical differences between ATG and CD34+ in terms of relapse [HR 1.52 (95% CI 0.96–2.42), p = 0.07], non-relapse mortality [HR 0.96 (95% CI 0.54–1.74), p = 0.90], overall survival [HR 1.43 (95% CI 0.97–2.11), p = 0.07], and leukemia-free survival [HR 1.25 (95% CI 0.88–1.78), p = 0.21]. Significantly, more deaths related to infection occurred in the CD34+ group (16/52 vs. 19/112, p = 0.04). Conclusions These data suggest that both ex vivo CD34-selected and in vivo ATG T cell depletion are associated with a rather high OS and should be compared in a prospective randomized trial.http://link.springer.com/article/10.1186/s13045-018-0668-3Acute myeloid leukemiaT cell depletionCD34-selected graftAntithymocyte globulinAllogeneic hematopoietic cell transplantation
collection DOAJ
language English
format Article
sources DOAJ
author Florent Malard
Myriam Labopin
Christina Cho
Didier Blaise
Esperanza B. Papadopoulos
Jakob Passweg
Richard O’Reilly
Edouard Forcade
Molly Maloy
Liisa Volin
Hugo Castro-Malaspina
Yosr Hicheri
Ann A. Jakubowski
Corentin Orvain
Sergio Giralt
Mohamad Mohty
Arnon Nagler
Miguel-Angel Perales
spellingShingle Florent Malard
Myriam Labopin
Christina Cho
Didier Blaise
Esperanza B. Papadopoulos
Jakob Passweg
Richard O’Reilly
Edouard Forcade
Molly Maloy
Liisa Volin
Hugo Castro-Malaspina
Yosr Hicheri
Ann A. Jakubowski
Corentin Orvain
Sergio Giralt
Mohamad Mohty
Arnon Nagler
Miguel-Angel Perales
Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
Journal of Hematology & Oncology
Acute myeloid leukemia
T cell depletion
CD34-selected graft
Antithymocyte globulin
Allogeneic hematopoietic cell transplantation
author_facet Florent Malard
Myriam Labopin
Christina Cho
Didier Blaise
Esperanza B. Papadopoulos
Jakob Passweg
Richard O’Reilly
Edouard Forcade
Molly Maloy
Liisa Volin
Hugo Castro-Malaspina
Yosr Hicheri
Ann A. Jakubowski
Corentin Orvain
Sergio Giralt
Mohamad Mohty
Arnon Nagler
Miguel-Angel Perales
author_sort Florent Malard
title Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
title_short Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
title_full Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
title_fullStr Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
title_full_unstemmed Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
title_sort ex vivo and in vivo t cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the alwp of the ebmt and the mskcc
publisher BMC
series Journal of Hematology & Oncology
issn 1756-8722
publishDate 2018-10-01
description Abstract Background Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors. Results Two-year overall survival estimate was 69.9% (95% CI, 58.5–69.4) in the ATG group and 67.6% (95% CI, 60.3–74.9) in the CD34+ group (p = 0.31). The cumulative incidence of grade II–IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1–3.7), p = 0.02; HR 15.1 (95% CI 5.3–42.2), p < 0.0001]. Parameters associated with a lower GVHD-free relapse-free survival (GRFS) were ATG [HR 1.6 (95% CI 1.1–2.2), p = 0.006], adverse cytogenetic [HR 1.7 (95% CI 1.3–2.2), p = 0.0004], and the use of an unrelated donor [HR 1.4 (95% CI 1.0–1.9), p = 0.02]. There were no statistical differences between ATG and CD34+ in terms of relapse [HR 1.52 (95% CI 0.96–2.42), p = 0.07], non-relapse mortality [HR 0.96 (95% CI 0.54–1.74), p = 0.90], overall survival [HR 1.43 (95% CI 0.97–2.11), p = 0.07], and leukemia-free survival [HR 1.25 (95% CI 0.88–1.78), p = 0.21]. Significantly, more deaths related to infection occurred in the CD34+ group (16/52 vs. 19/112, p = 0.04). Conclusions These data suggest that both ex vivo CD34-selected and in vivo ATG T cell depletion are associated with a rather high OS and should be compared in a prospective randomized trial.
topic Acute myeloid leukemia
T cell depletion
CD34-selected graft
Antithymocyte globulin
Allogeneic hematopoietic cell transplantation
url http://link.springer.com/article/10.1186/s13045-018-0668-3
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