Abstract
An increasing number of older patients with acute myeloid leukemia (AML) are offered an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Normally, older patients have older matched related donors (MRD). Matched unrelated donors (MUD) are an important alternative, but it remains unclear whether a younger MUD is associated with better outcomes, especially in the context of post-transplant cyclophosphamide (PTCy). We compared outcomes of patients older than 50 years with AML in first complete remission (CR1) and receiving a first HSCT from a 10/10 MUD aged younger than 40 years to those receiving a graft from a MRD aged older than 50 years, using PTCy and with well-known transplant conditioning intensity (TCI) score. A total of 345 consecutive patients were included and classified according to TCI score as low, intermediate, or high. On multivariable analysis in the TCI-intermediate/high group, MUD was associated with better graft-versus-host disease-free, relapse-free survival, lower non-relapse mortality and lower relapse incidence. For patients receiving a TCI-low regimen, outcomes are independent on the type of donor. In patients with AML in CR1, older than 50 years and receiving a TCI-intermediate/high conditioning regimen using PTCy, a MUD younger than 40 years is preferable over a MRD older than 50 years.
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Data availability
The dataset supporting the conclusions of this article is available from the ALWP of the EBMT at the Saint Antoine Hospital, Paris.
References
Li X, Zeng X, Xu Y, Wang B, Zhao Y, Lai X, et al. Mechanisms and rejuvenation strategies for aged hematopoietic stem cells. J Hematol Oncol. 2020;13:31.
Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371:2488–98.
Kollman C, Spellman SR, Zhang MJ, Hassebroek A, Anasetti C, Antin JH, et al. The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy. Blood. 2016;127:260–7.
DeZern AE, Franklin C, Tsai HL, Imus PH, Cooke KR, Varadhan R, et al. Relationship of donor age and relationship to outcomes of haploidentical transplantation with posttransplant cyclophosphamide. Blood Adv. 2021;5:1360–8.
Ambinder A, Jain T, Tsai HL, Horowitz MM, Jones RJ, Varadhan R. HLA-matching with PTCy: a reanalysis of a CIBMTR dataset with propensity score matching and donor age. Blood Adv. 2022;6:4335–46.
Wang Y, Wu DP, Liu QF, Xu LP, Liu KY, Zhang XH, et al. Donor and recipient age, gender and ABO incompatibility regardless of donor source: validated criteria for donor selection for haematopoietic transplants. Leukemia. 2018;32:492–8.
Alousi AM, Le-Rademacher J, Saliba RM, Appelbaum FR, Artz A, Benjamin J, et al. Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer? Blood. 2013;121:2567–73.
Peffault de Latour R, Labopin M, Cornelissen J, Vigouroux S, Craddock C, Blaise D, et al. In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available? Bone Marrow Transpl. 2015;50:1411–5.
Guru Murthy GS, Kim S, Hu ZH, Estrada-Merly N, Abid MB, Aljurf M, et al. Relapse and disease-free survival in patients with myelodysplastic syndrome undergoing allogeneic hematopoietic cell transplantation using older matched sibling donors vs. younger matched unrelated donors. JAMA Oncol. 2022;8:404–11.
Abid MB, Estrada-Merly N, Zhang MJ, Chen K, Allan D, Bredeson C, et al. Impact of donor age on allogeneic hematopoietic cell transplantation outcomes in older adults with Acute Myeloid Leukemia. Transpl Cell Ther. 2023;29:578.e1–578.e9.
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 Transpl. 2016;51:610–1.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.
Lee SJ, Vogelsang G, Flowers MED. Chronic graft-versus-host disease. Biol Blood Marrow Transpl. 2003;9:215–33.
Spyridonidis A, Labopin M, Savani BN, Niittyvuopio R, Blaise D, Craddock C, et al. Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients. Bone Marrow Transpl. 2020;55:1114–25.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
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.
Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163–70.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.
Cox DR. Regression models and life-tables. J R Stat Soc Ser B. 1972;34:187–220.
D’Souza A, Fretham C, Lee SJ, Arora M, Brunner J, Chhabra S, et al. Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transpl. 2020;26:e177–82.
Montoro J, Piñana JL, Hernández-Boluda JC, Hernani R, Lorenzo I, Pérez A, et al. Uniform graft-versus-host disease prophylaxis with posttransplant cyclophosphamide, sirolimus, and mycophenolate mofetil following hematopoietic stem cell transplantation from haploidentical, matched sibling and unrelated donors. Bone Marrow Transpl. 2020;55:2147–59.
Sanz J, Galimard J-E, Labopin M, Afanasyev B, Angelucci E, Ciceri F, et al. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT. J Hematol Oncol. 2020;13:46.
Piemontese S, Lupo Stanghellini MT, Sora F, Sica S, Peccatori J, Marcatti M, et al. Post-transplant cyclophosphamide with Sirolimus or Cyclosporine for GvHD prophylaxis in matched related and unrelated transplantation: a two-center analysis on 213 consecutive patients. Bone Marrow Transpl. 2024;59:692–4.
Bolaños-Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. N Engl J Med. 2023;388:2338–48.
Spyridonidis A, Labopin M, Gedde-Dahl T, Ganser A, Stelljes M, Craddock C, et al. Validation of the transplant conditioning intensity (TCI) index for allogeneic hematopoietic cell transplantation. Bone Marrow Transpl. 2024;59:217–23.
Abid MB, Estrada-Merly N, Zhang MJ, Chen K, Bredeson C, Allan D, et al. Younger matched unrelated donors confer decreased relapse risk compared to older sibling donors in older patients with B cell acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation. Transpl Cell Ther. 2023;29:611–8.
Marcoux C, Marin D, Ramdial J, AlAtrash G, Alousi AM, Oran B, et al. Younger haploidentical donor versus older matched unrelated donor for patients with AML/MDS. Am J Hematol. 2023;98:712–9.
Shaw BE, Logan BR, Spellman SR, Marsh SGE, Robinson J, Pidala J, et al. Development of an unrelated donor selection score predictive of survival after HCT: donor age matters most. Biol Blood Marrow Transpl. 2018;24:1049–56.
Acknowledgements
This study was conducted on behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). We thank all data managers from the ALWP who collected and checked data. We thank all EBMT centers for contributing patients to the study. This study was supported by the EBMT funded by annual subscription from the constituent transplant centers.
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SP, ML, MM, JS and FC: designed the study. ML: performed statistical analysis and helped with the interpretation of the results. SP: wrote the manuscript. GC, AECB, JP, EM, GVG, MR, MJPC, SS, JV, AK, AB, JS, FC: provided patients for the study. All authors reviewed and approved the manuscript.
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The scientific board of the ALWP of the EBMT approved this study. All patients gave written informed consent for the use of their data.
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Piemontese, S., Labopin, M., Choi, G. et al. Older MRD vs. younger MUD in patients older than 50 years with AML in remission using post-transplant cyclophosphamide. Leukemia 38, 2016–2022 (2024). https://doi.org/10.1038/s41375-024-02359-8
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DOI: https://doi.org/10.1038/s41375-024-02359-8


