Stem cell transplantation from a haploidentical donor versus a genoidentical sister for adult male patients with acute myelogenous leukemia in first remission: A retrospective study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation.
Adolescent
Adult
Aged
Bone Marrow
/ chemistry
Female
Follow-Up Studies
Graft vs Host Disease
/ prevention & control
Hematopoietic Stem Cell Transplantation
/ methods
Humans
Leukemia, Myeloid, Acute
/ pathology
Male
Middle Aged
Prognosis
Remission Induction
Retrospective Studies
Risk Assessment
/ statistics & numerical data
Siblings
Survival Rate
Tissue Donors
/ supply & distribution
Transplantation, Haploidentical
/ methods
Transplantation, Homologous
Young Adult
acute myeloid leukemia
haploidentical donors
matched sibling donors
stem cell transplantation
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
received:
28
05
2019
revised:
14
09
2019
accepted:
19
09
2019
pubmed:
28
11
2019
medline:
21
10
2020
entrez:
28
11
2019
Statut:
ppublish
Résumé
In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs. In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics. Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10 In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice.
Sections du résumé
BACKGROUND
In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs.
METHODS
In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics.
RESULTS
Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10
CONCLUSIONS
In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice.
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1004-1015Informations de copyright
© 2019 American Cancer Society.
Références
Gragert L, Eapen M, Williams E, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371:339-348.
Salvatore D, Labopin M, Ruggeri A, et al. Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2018;103:1317-1328.
Battipaglia G, Boumendil A, Labopin M, et al. Unmanipulated haploidentical versus HLA-matched sibling allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute myeloid leukemia: a retrospective study on behalf of the ALWP of the EBMT. Bone Marrow Transplant. 2019;54:1499-1510.
Rashidi A, Hamadani M, Zhang MJ, et al. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission. Blood Adv. 2019;3:1826-1836.
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.
Gorin NC, Labopin M, Polge E, et al. Risk assessment in adult acute lymphoblastic leukaemia before early haemopoietic stem cell transplantation with a geno-identical donor: an easy clinical prognostic score to identify patients who benefit most from allogeneic haemopoietic stem cell transplantation. Leukemia. 2003;17:1596-1599.
Loren AW, Bunin GR, Boudreau C, et al. Impact of donor and recipient sex and parity on outcomes of HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2006;12:758-769.
Kim HT, Zhang MJ, Woolfrey AE, et al. Donor and recipient sex in allogeneic stem cell transplantation: what really matters. Haematologica. 2016;101:1260-1266.
Baron F, Labopin M, Ruggeri A, et al. Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood-a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation. J Hematol Oncol. 2015;6:107.
Miklos DB, Kim HT, Miller KH, et al. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood. 2005;105:2973-2978.
Popli R, Sahaf B, Nakasone H, Lee JY, Miklos DB. Clinical impact of H-Y alloimmunity. Immunol Res. 2014;58(2-3):249-258.
Luznik L, Engstrom LW, Iannone R, Fuchs EJ. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol Blood Marrow Transplant. 2002;8:131-138.
Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641-650.
Luznik L, Bolanos-Meade J, Zahurak M, et al. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010;115:3224-3230.
Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:132.
Kanakry JA, Luznik L. Might haplo “be the (better) match?” Blood. 2016;127:799-800.
Huang XJ, Liu DH, Liu KY, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant. 2006;38:291-297.
Passweg JR, Baldomero H, Bader P, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant. 2017;52:811-817.
Ciurea SO, Zhang MJ, Bacigalupo AA, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033-1040.
Lorentino F, Labopin M, Bernardi M, et al. Comparable outcomes of haploidentical, 10/10 and 9/10 unrelated donor transplantation in adverse karyotype AML in first complete remission. Am J Hematol. 2018;93:1236-1244.
Pagliardini T, Harbi S, Furst S, et al. Post-transplantation cyclophosphamide-based haploidentical versus Atg-based unrelated donor allogeneic stem cell transplantation for patients younger than 60 years with hematological malignancies: a single-center experience of 209 patients. Bone Marrow Transplant. 2019;54:1067-1076.
Giannotti F, Labopin M, Shouval R, et al. Haploidentical transplantation is associated with better overall survival when compared with single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine. J Hematol Oncol. 2018;11:110.
Ruggeri A, Labopin M, Savani B, et al. Hematopoietic stem cell transplantation with unrelated cord blood or haploidentical donor grafts in adult patients with secondary acute myeloid leukemia, a comparative study from Eurocord and the ALWP EBMT [published online May 31, 2019]. Bone Marrow Transplant. doi:10.1038/s41409-019-0582-5
Gu B, Zhang X, Chen G, et al. Efficacy of haploidentical hematopoietic stem cell transplantation compared to HLA-matched transplantation for primary refractory acute myeloid leukemia. Ann Hematol. 2018;97:2185-2194.
Marani C, Raiola AM, Morbelli S, et al. Haploidentical transplants with post-transplant cyclophosphamide for relapsed or refractory Hodgkin lymphoma: the role of comorbidity index and pretransplant positron emission tomography. Biol Blood Marrow Transplant. 2018;24:2501-2508.
Yu WJ, Wang Y, Xu LP, Zhang XH, Liu KY, Huang XJ. [Influence of donor-recipient sex matching on outcomes of haploidentical hematopoietic stem cell transplantation for acute leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2018;39:398-403.
McCurdy SR, Zhang MJ, St Martin A, et al. Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide. Blood Adv. 2018;2:299-307.
Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628-1633.
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.
Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825-858.
Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9:215-233.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-481.
Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695-706.
Cox DR. Regression models and life tables. J R Stat Soc. 1972;34:187-202.
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.
Aversa F, Martelli MF, Velardi A. Haploidentical hematopoietic stem cell transplantation with a megadose T-cell-depleted graft: harnessing natural and adaptive immunity. Semin Oncol. 2012;39:643-652.
Huang XJ, Zhu HH, Chang YJ, et al. The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission. Blood. 2012;119:5584-5590.
Gorin NC, Labopin M, Piemontese S, et al. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis. Haematologica. 2015;100:558-564.
Passweg JR, Baldomero H, Bader P, et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40,000 transplants annually. Bone Marrow Transplant. 2016;51:786-792.
Cazin B, Gorin NC, Laporte JP, et al. Cardiac complications after bone marrow transplantation. A report on a series of 63 consecutive transplantations. Cancer. 1986;57:2061-2069.
Dulery R, Mohty M, Labopin M, et al. Features and outcome of early cardiac toxicity associated with post-transplant cyclophosphamide in allogeneic stem cell transplantation. Abstracts from the 45th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2019;54(suppl):69-70.
Ruggeri A, Roth-Guepin G, Battipaglia G, et al. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transplant Infect Dis. 2015;17:822-830.
Bashey A, Zhang X, Jackson K, et al. Comparison of outcomes of hematopoietic cell transplants from T-replete haploidentical donors using post-transplantation cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors and HLA-identical sibling donors: a multivariable analysis including disease risk index. Biol Blood Marrow Transplant. 2016;22:125-133.
Martinez C, Gayoso J, Canals C, et al. Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for Hodgkin lymphoma: a registry study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation. J Clin Oncol. 2017;35:3425-3432.
Dholaria B, Savani BN, Labopin M, et al. Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT [published online September 19, 2019]. Haematologica. doi:10.3324/haematol.2019.219790
Robinson TM, Fuchs EJ, Zhang MJ, et al. Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch? Blood Adv. 2018;2:1180-1186.
Ringden O, Labopin M, Ciceri F, et al. Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings? Leukemia. 2016;30:447-455.
Shimoni A, Labopin M, Angelucci E, et al. Graft-versus-leukemia effect after haplo-identical stem cell transplantation with post-transplant cyclophosphamide in patients with AML-no association with graft-versus-host disease: a study on behalf of the Acute Leukemia Working Party of EBMT. Biol Bone Marrow Transplant. 2019;25(suppl):S242-S243.