We compared transplantation (HSCT) outcomes in AML patients undergoing HSCT with post-transplant cyclophosphamide (PTCy) in first complete remission from 1065 young (<35 years) haploidentical (Haplo) donors (yHaplo) vs. 147 old (≥35 years) mismatched unrelated donors (oMMUD) (first comparison) and from 271 young (<35 years) MMUD (yMMUD) vs. 1315 old (≥35 years) Haplo donors (oHaplo) (second comparison). Acute graft-versus-host disease (aGVHD) grades II-IV were significantly lower in the yHaplo vs. oMMUD group (HR = 0.62, p = 0.007). There were no significant differences in chronic GVHD, non-relapse mortality (NRM), relapse incidence, leukemia-free survival, overall survival, and GVHD-free and relapse-free survival. As for the second comparison, more patients in the oHaplo group had de novo AML, 86.6% vs. 81.9% in the yMMUD group (p = 0.044), while myeloablative conditioning was used more frequently in the yMMUD group, 53.3% vs. 46.8% in the oHaplo group (p = 0.049). aGVHD grades II-IV and NRM were significantly lower in the yMMUD vs. oHaplo group (HR = 0.69, p = 0.013 and HR = 0.60, p = 0.022). All other transplant outcomes did not differ. In conclusion, HSCT from young alternative donors (<35 years) results in a lower incidence of grades II-IV aGVHD. In addition, NRM is lower in HSCT from yMMUD compared to HSCT from oHaplo.

Department of Hematology EBMT Paris Study Office Saint Antoine Hospital INSERM UMR 938 Sorbonne University Paris France

Department of Hematology Hospital General Universitario Gregorio Marañon Institute of Health Research Gregorio Marañon Madrid Spain

Department of Hematology Saint Antoine Hospital INSERM UMR 938 Sorbonne University Paris France

Dipartimento di Diagnostica per Immagini Radioterapia Oncologica ed Ematologia Fondazione Policlinico Universitario A Gemelli IRCCS Università Cattolica Sacro Cuore Rome Italy

Division of Hematology Sheba Medical Center Tel Hashomer Israel

Hospital Clínico Salamanca Spain

Institute of Hematology and Blood Transfusion Prague Czech Republic

IRCCS Osspedale San Raffaele Vita Salute San Raffaele University Hematology and BMT Milano Italy

Maria Sklodowska Curie National Research Institute of Oncology Gliwice Branch Gliwice Poland

Medicana International Hospital Istanbul Istanbul Turkey

Ospedale San Raffaele s r l Milano Italy

Programme de Transplantation and Therapie Cellulaire Marseille France

RM Gorbacheva Research Institute Pavlov University Petersburg Russian Federation

S S C 5 D Trapianto di Cellule Staminali Torino Italy

Stem Cell Transplantation and Cellular Therapies Unit Department of Hemato Oncology and Radiotherapy Grande Ospedale Metropolitano Bianchi Melacrino Morelli Reggio Calabria Italy

Transplantation Unit Department of Oncology and Haematology IRCCS Humanitas Research Hospital Milan Italy

Turku University Hospital Turku Finland

Zobrazit více v PubMed

Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel. Blood. 2022;140:1345–77. PubMed DOI

Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnostic, risk-stratification, and management. Am J Hematol. 2023;98:502–26. PubMed DOI

Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110:4576–83. PubMed DOI

Shouval R, Fein JA, Labopin M, Kroger N, Duarte RF, Bader P, et al. Outcomes of allogeneic hematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 2019;6:e573–e584. PubMed DOI

Fleischhauer K, Tran TH, Meisel R, Mytilineos J, Dreger P, Kröger N. Donor selection for allogeneic hematopoietic cell transplantation. Dtsch Arztebl Int. 2023;120:261–8. PubMed PMC

Savani BN, Labopin M, Kröger N, Finke J, Ehninger G, Niederwieser D, et al. Expanding transplant options to patients over 50 years. Improved outcome after reduced-intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT. Haematologica. 2016;101:773–80. PubMed DOI PMC

Loke J, Labopin M, Craddock C, Niederwieser D, Cornelissen J, Afansayev B, et al. Impact of patient: donor HLA disparity on reduced-intensity-conditioned allogeneic stem cell transplants from HLA mismatched unrelated donors for AML: from the ALWP of the EBMT. Bone Marrow Transplant. 2021;56:614–21. PubMed DOI

Nagler A, Dholaria B, Labopin M, Bruno B, Rambaldi A, Pioltelli P, et al. The outcome of two or more HLA loci mismatched unrelated donor hematopoietic cell transplantation for acute leukemia: an ALWP of the EBMT study. Bone Marrow Transplant. 2021;56:20–29. PubMed DOI

Kollman C, Howe CW, Anasetti C, Antin JH, Davies SM, Filipovich AH, et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood. 2001;98:2043–51. PubMed DOI

Bastida JM, Cabrero M, Lopez-Godino O, Lopez- Para M, Sanchez-Guijo F, Lopez- Corral L, et al. Influence of donor age in allogeneic stem cell transplant outcome in acute myeloid leukemia and myelodisplastic syndrome. Leuk Res. 2015;39:828–34. PubMed DOI

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. PubMed DOI PMC

Canaani J, Savani BN, Labopin M, Huang XJ, Ciceri F, Arcese W, et al. Donor age determines outcome in acute leukemia patients over 40 undergoing haploidentical hematopoietic cell transplantation. Am J Hematol. 2018;93:246–53. PubMed DOI

Chang YJ, Luznik L, Fuchs EJ, Huang XJ. How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation? J Hematol Oncol. 2016;12:35. DOI

Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, et al. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood. 2011;118:2609–17. PubMed DOI

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. PubMed DOI PMC

Ciurea SO, Champlin RE. Donor selection in T cell-replete haploidentical hematopoietic stem cell transplantation: knowns, unknowns, and controversies. Biol Blood Marrow Transplant. 2013;19:180–4. PubMed DOI

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. PubMed DOI PMC

Sanz J, Labopin M, Blaise D, Raiola AM, Busca A, Vydra J, et al. Haploidentical stem cell donor choice for patients with acute myeloid leukemia: a study from the ALWP of the EBMT. Blood Adv. 2024;8:2332–41. PubMed DOI PMC

Kröger N, Zabelina T, de Wreede L, Berger J, Alchalby H, Van Biezen A, et al. Allogeneic stem cell transplantation for older advanced MDS patients: improved survival with young unrelated donor in comparison with HLA-identical siblings. Leukemia. 2013;27:604–9. PubMed DOI

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. PubMed DOI PMC

Murthy GSG, 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. PubMed DOI PMC

McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolaños-Meade J, Rosner GL, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125:3024–31. PubMed DOI PMC

Kasamon YL, Bolaños-Meade J, Prince GT, Tsai HL, McCurdy SR, Kanakry JA, et al. Outcomes of nonmyeloablative HLA-haploidentical blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in older adults. J Clin Oncol. 2015;33:3152–61. PubMed DOI PMC

Shaw BE, Jimenez-Jimenez AM, Burns LJ, Logan BR, Khimani F, Shaffer BC, et al. National marrow donor program-sponsored multicenter, phase II trial of HLA-mismatched unrelated donor bone marrow transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2021;39:1971–82. PubMed DOI PMC

Battipaglia G, Galimard JE, Labopin M, Raiola AM, Blaise D, Ruggeri A, et al. Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant. 2022;57:562–71. PubMed DOI

Baron F, Labopin M, Tischer J, Ciceri F, Raiola AM, Blaise D, et al. Comparison of HLA-mismatched unrelated donor transplantation with post-transplant cyclophosphamide versus HLA-haploidentical transplantation in patients with active acute myeloid leukemia. Bone Marrow Transplant. 2022;57:1657–63. PubMed DOI

Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–40. PubMed DOI PMC

Rashidi A, Hamadani M, Zhang MJ, Wang HL, Abdel-Azim H, Aljurf M, et al. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission. Blood Adv. 2019;3:1826–36. PubMed DOI PMC

Gooptu M, Romee R, St Martin A, Arora M, Al Malki M, Antin JH, et al. HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis. Blood. 2021;138:273–82. PubMed DOI PMC

Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33. PubMed DOI PMC

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8. PubMed

Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17. PubMed DOI

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;51:610–1. PubMed DOI

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. 2019;2:2–4. PubMed DOI PMC

Andersen PK, Klein JP, Zhang MJ. Testing for center effects in multi-center survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18:1489–500. PubMed DOI

R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing; 2020. https://www.R-project.org/ .

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 Transplant. 2018;24:1049–56. PubMed DOI PMC

Rezvani AR, Storer BE, Guthrie KA, Schoch HG, Maloney DG, Sandmaier BM, et al. Impact of donor age on outcome after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21:105–12. PubMed DOI

Nagler A, Labopin M, Mielke S, Passweg J, Blaise D, Gedde-Dahl T, et al. Matched related versus unrelated versus haploidentical donors for allogeneic transplantation in AML patients achieving first complete remission after two induction courses: a study from the ALWP/EBMT. Bone Marrow Transplant. 2023;58:791–800. PubMed DOI

Al Hamed R, Ngoya M, Galimard JE, Sengeloev H, Gedde-Dahl T, Kulagin A, et al. Unrelated or haploidentical allogeneic hematopoietic cell transplantation in second complete remission for acute myeloid leukemia—Improved outcomes over time: A European Society for Blood and Marrow Transplantation Acute Leukemia Working Party study. Cancer. 2023;129:2645–54. PubMed DOI

Rockstroh A, Al-Ali HK, Lange T, Pönisch W, Krahl R, Cross M, et al. Comparable outcome after single-antigen-mismatched versus matched unrelated donor haematopoietic cell transplantation. J Cancer Res Clin Oncol. 2015;141:2193–203. PubMed DOI

Lorentino F, Labopin M, Ciceri F, Vago L, Fleischhauer K, Afanasyev B, et al. Post-transplantation cyclophosphamide GvHD prophylaxis after hematopoietic stem cell transplantation from 9/10 or 10/10 HLA-matched unrelated donors for acute leukemia. Leukemia. 2021;35:585–94. PubMed DOI

Robinson TM, Fuchs EJ, Zhang MJ, St Martin A, Labopin M, Keesler DA, et al. Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch? Acute Leukemia Working Party of the European Society for Blood and Marrow Transplant and the Center for International Blood and Marrow Transplant Research. Blood Adv. 2018;2:1180–6. PubMed DOI PMC

Marcoux C, Marin D, Ramdial J, Al Atrash 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. PubMed DOI

Mehta RS, Ramdial J, Marin D, Alousi A, Kanakry CG, Champlin RE, et al. Impact of donor age in haploidentical-post-transplantation cyclophosphamide versus matched unrelated donor post-transplantation cyclophosphamide hematopoietic stem cell transplantation in patients with acute myeloid leukemia. Transplant Cell Ther. 2023;29:377.e1–377.e7. PubMed DOI

Nagler A, Labopin M, Blaise D, Raiola AM, Corral LL, Bramanti S, et al. Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT. J Hematol Oncol. 2023;16:58. PubMed DOI PMC