Post-transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA-identical sibling donors: A retrospective analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
Adolescent
Adult
Aged
Antilymphocyte Serum
/ administration & dosage
Blood Donors
Cyclophosphamide
/ administration & dosage
Feasibility Studies
Female
Follow-Up Studies
Graft vs Host Disease
/ epidemiology
HLA Antigens
/ immunology
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Immunosuppressive Agents
/ administration & dosage
Incidence
Leukemia, Myeloid, Acute
/ surgery
Male
Middle Aged
Retrospective Studies
Siblings
Transplantation, Homologous
/ methods
Treatment Outcome
Young Adult
acute myeloid leukemia
allogeneic hematopoietic transplantation
antithymocyte globulin
graft-versus-host disease
post-transplantation cyclophosphamide
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
28
05
2020
revised:
24
06
2020
accepted:
16
07
2020
pubmed:
30
10
2020
medline:
28
8
2021
entrez:
29
10
2020
Statut:
ppublish
Résumé
Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Addition of antithymocyte globulin (ATG) or post-transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings. We compared the outcomes of adults with acute myeloid leukemia undergoing allo-HSCT from HLA-identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913). Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P < .01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P < .01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P < .01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P < .01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P < .02). PTCY is feasible in an HLA-identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD.
Sections du résumé
BACKGROUND
Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Addition of antithymocyte globulin (ATG) or post-transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings.
METHODS
We compared the outcomes of adults with acute myeloid leukemia undergoing allo-HSCT from HLA-identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913).
RESULTS
Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P < .01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P < .01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P < .01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P < .01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P < .02).
CONCLUSION
PTCY is feasible in an HLA-identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD.
Substances chimiques
Antilymphocyte Serum
0
HLA Antigens
0
Immunosuppressive Agents
0
Cyclophosphamide
8N3DW7272P
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
209-218Informations de copyright
© 2020 American Cancer Society.
Références
Deeg HJ, Lin D, Leisenring W, et al. Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial. Blood. 1997;89:3880-3887.
Ringdén O, Labopin M, Bacigalupo A, et al. Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia. J Clin Oncol. 2002;20:4655-4664.
Hahn T, McCarthy PL Jr, Zhang MJ, et al. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol. 2008;26:5728-5734.
Kröger N, Solano C, Wolschke C, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med. 2016;374:43-53.
Mohty M, Faucher C, Vey N, et al. High rate of secondary viral and bacterial infections in patients undergoing allogeneic bone marrow mini-transplantation. Bone Marrow Transplant. 2000;26:251-255.
Soiffer RJ, Lerademacher J, Ho V, et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117:6963-6970.
Luznik L, O’Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641-650.
El Fakih R, Hashmi SK, Ciurea SO, Luznik L, Gale RP, Aljurf M. Post-transplant cyclophosphamide use in matched HLA donors: a review of literature and future application. Bone Marrow Transplant. 2020;55:40-47.
Ruggeri A, Labopin M, Bacigalupo A, et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018;11:40.
Battipaglia G, Labopin M, Kröger N, et al. Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood. 2019;134:892-899.
Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116:354-365.
Jethava YS, Sica S, Savani B, et al. Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemia. Bone Marrow Transplant. 2017;52:1504-1511.
Przepiorka D, Chan KW, Champlin RE, et al. Prevention of graft-versus-host disease with anti-CD5 ricin A chain immunotoxin after CD3-depleted HLA-nonidentical marrow transplantation in pediatric leukemia patients. Bone Marrow Transplant. 1995;16:737-741.
Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100:406-414.
Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission. Bone Marrow Transplant. 2016;51:610-611.
Kaplan EL, Mayer P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 2008;53:457-481.
Kanate AS, Nagler A, Savani B. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2020;2:2-4.
Fine JP, Gray RJ. A Proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 2009;446:496-509.
Ho D, Imai K, King G, et al. Matching as non-parametric preprocessing for reducing model dependence in parametric causal inference. Political Analysis. 2007;15:199-236.
Passweg JR, Baldomero H, Peters C, et al. Hematopoietic SCT in Europe: data and trends in 2012 with special consideration of pediatric transplantation. Bone Marrow Transplant. 2014;49:744-750.
Hamilton BK, Rybicki L, Dean R, et al. Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA-identical sibling donor allogeneic hematopoietic cell transplantation. Am J Hematol. 2015;90:144-148.
Piñana JL, Valcárcel D, Fernández-Avilés F, et al. MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings. Bone Marrow Transplant. 2010;45:1449-1456.
Nagler A, Labopin M, Shimoni A, et al. Mobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012;18:1422-1429.
Shimony O, Nagler A, Gellman YN, et al. Anti-T lymphocyte globulin (ATG) induces generation of regulatory T cells, at least part of them express activated CD44. J Clin Immunol. 2012;32:173-188.
Fang L, Fehse B, Engel M, Zander A, Kröger N. Antithymocyte globulin induces ex vivo and in vivo depletion of myeloid and plasmacytoid dendritic cells. Transplantation. 2005;79:369-371.
McCurdy SR, Luznik L. Post-transplantation cyclophosphamide for chimerism-based tolerance. Bone Marrow Transplant. 2019;54:769-774.
Devillier R, Labopin M, Chevallier P, et al. Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of European Group of Bone Marrow Transplantation. Bone Marrow Transplant. 2018;53:431-437.
Baron F, Mohty M, Blaise D, et al. Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2017;102:224-234.
Walker I, Panzarella T, Couban S, et al. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2020;7:e100-e111.
Baron F, Galimard JE, Labopin M, et al. Allogeneic peripheral blood stem cell transplantation with anti-thymocyte globulin versus allogeneic bone marrow transplantation without anti-thymocyte globulin. Haematologica. 2020;105:1138-1146.
Bradstock KF, Bilmon I, Kwan J, et al. Single-agent high-dose cyclophosphamide for graft-versus-host disease prophylaxis in human leukocyte antigen-matched reduced-intensity peripheral blood stem cell transplantation results in an unacceptably high rate of severe acute graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21:941-944.
Kanakry CG, O’Donnell PV, Furlong T, et al. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014;32:3497-3505.
Saraceni F, Labopin M, Forcade E, et al. Allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and Karnofsky performance status score equal or lower than 80%. A study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Blood. 2019;134(suppl 1):2038.
Broers AE, van Der Holt R, van Esser JW, et al. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation. Blood. 2000;95:2240-2245.
Gratwohl A, Hermans J, Niederwieser D, van Biezen A, van Houwelingen HC, Apperley J. Female donors influence transplant-related mortality and relapse incidence in male recipients of sibling blood and marrow transplants. Hematol J. 2001;2:363-370.