{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:39:39Z","timestamp":1789832379132,"version":"4.0.1"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"\n Importance<\/jats:title>\n Advanced age in unrelated donors (URDs) is a well-established risk factor in allogeneic hematopoietic cell transplant (HCT), leading registries to prioritize younger donors. However, this paradigm relevance is uncertain in the era of posttransplant cyclophosphamide (PTCy) for graft-vs-host disease (GVHD) prophylaxis, a strategy increasingly adopted for its effectiveness. Clarifying this association is crucial for optimizing donor selection and potentially expanding the donor pool.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine whether the association of older URD age with overall survival differs between patients receiving PTCy-based vs conventional calcineurin inhibitor (CNI)\u2212based GVHD prophylaxis.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a multicenter cohort study using registry data from the Center for International Blood and Marrow Transplant Research for January 2017 through June 2021. Eligible participants were adult patients with acute leukemia or myelodysplastic syndrome who underwent an allogeneic HCT from a URD who was fully matched for 8 of 8 human leukocyte antigen loci (MUD) or mismatched for 7 of 8 human leukocyte antigen loci (MMUD). Data were analyzed from January to June 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n GVHD prophylaxis regimen (PTCy-based vs CNI-based) and donor age (analyzed continuously and categorically).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Overall survival was the primary outcome, with associations assessed using a multipronged approach including least absolute shrinkage and selection operator (LASSO)\u2212penalized Cox proportional hazards models, inverse probability of treatment weighting (IPTW), and XGBoost machine learning.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The study analysis included 10\u202f025 patients (mean [SD] age, 56.5 [14.4] years; 4379 female [43.7%] and 5646 male [56.3%] individuals) among whom 7272 (72.5%) had received MUD-CNI; 1681 (16.8%%) MUD-PTCy; 613 (6.1%) MMUD-PTCy; and 459 (4.6%) MMUD-CNI. Increasing donor age was associated with worse OS in CNI-based MUD (hazard ratio [HR], 1.004-1.009 per year increase) and MMUD (HR, 1.022-1.034) cohorts. Conversely, this association was not observed in the combined PTCy cohort (HR, 1.001-1.007). These findings were robust across standard and overlap weighted IPTW, LASSO-penalized models, and XGBoost analyses. The attenuated association in the PTCy cohort was primarily driven by a lack of association between donor age and nonrelapse mortality.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The findings of this cohort study indicate that the association of donor age with URD HCT outcomes appears to be mitigated in the PTCy setting, suggesting that PTCy may counteract some of the adverse effects associated with increased unrelated donor age. This observation challenges existing paradigms and warrants validation in independent cohorts, and if validated, could substantially expand the donor pool.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2025.4551","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T16:31:12Z","timestamp":1762446672000},"page":"28","source":"Crossref","is-referenced-by-count":10,"title":["Unrelated Donor Age and Recipient Outcomes After Posttransplant Cyclophosphamide vs Conventional Prophylaxis"],"prefix":"10.1001","volume":"12","author":[{"given":"Rohtesh S.","family":"Mehta","sequence":"first","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney A.","family":"Sparapani","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Kanakry","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon R.","family":"McCurdy","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2212Oncology, Department of Medicine, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Saultz","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2212Oncology, Oregon Health and Science University, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr","family":"Lazaryan","sequence":"additional","affiliation":[{"name":"Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Milano","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"2","key":"coi250067r1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1182\/blood-2015-08-663823","article-title":"The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy.","volume":"127","author":"Kollman","year":"2016","journal-title":"Blood"},{"issue":"5","key":"coi250067r2","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.bbmt.2018.02.006","article-title":"Development of an unrelated donor selection score predictive of survival after HCT: donor age matters most.","volume":"24","author":"Shaw","year":"2018","journal-title":"Biol Blood Marrow Transplant"},{"key":"coi250067r3","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1200\/CCI.20.00185","article-title":"Optimal donor selection for hematopoietic cell transplantation using Bayesian machine learning.","volume":"5","author":"Logan","year":"2021","journal-title":"JCO Clin Cancer Inform"},{"issue":"23","key":"coi250067r4","doi-asserted-by":"crossref","first-page":"6082","DOI":"10.1182\/bloodadvances.2024013756","article-title":"Novel machine learning technique further clarifies unrelated donor selection to optimize transplantation outcomes.","volume":"8","author":"Spellman","year":"2024","journal-title":"Blood Adv"},{"issue":"28","key":"coi250067r6","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1200\/JCO.24.00184","article-title":"Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis attenuates disparity in outcomes between use of matched or mismatched unrelated donors.","volume":"42","author":"Shaffer","year":"2024","journal-title":"J Clin Oncol"},{"issue":"24","key":"coi250067r8","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1182\/blood.2023023697","article-title":"Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT.","volume":"143","author":"Sanz","year":"2024","journal-title":"Blood"},{"issue":"6","key":"coi250067r9","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1172\/JCI124218","article-title":"Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression.","volume":"129","author":"Wachsmuth","year":"2019","journal-title":"J Clin Invest"},{"key":"coi250067r10","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.796349","article-title":"Post-transplantation cyclophosphamide uniquely restrains alloreactive CD4+ T-cell proliferation and differentiation after murine MHC-haploidentical hematopoietic cell transplantation.","volume":"13","author":"Hadjis","year":"2022","journal-title":"Front Immunol"},{"issue":"7","key":"coi250067r11","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1182\/bloodadvances.2022007026","article-title":"Posttransplantation cyclophosphamide expands functional myeloid-derived suppressor cells and indirectly influences Tregs.","volume":"7","author":"Fletcher","year":"2023","journal-title":"Blood Adv"},{"issue":"25","key":"coi250067r12","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1056\/NEJMoa2215943","article-title":"Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis.","volume":"388","author":"Bola\u00f1os-Meade","year":"2023","journal-title":"N Engl J Med"},{"issue":"6","key":"coi250067r13","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1038\/s41375-024-02256-0","article-title":"Improved survival with younger HLA-matched unrelated donors versus older matched sibling donor HCT with PTCy-prophylaxis.","volume":"38","author":"Ramdial","year":"2024","journal-title":"Leukemia"},{"issue":"9","key":"coi250067r15","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1182\/bloodadvances.2024012669","article-title":"Combined effect of unrelated donor age and HLA peptide-binding motif match status on HCT outcomes.","volume":"8","author":"Mehta","year":"2024","journal-title":"Blood Adv"},{"key":"coi250067r5","doi-asserted-by":"crossref","unstructured":"Cusatis? R, Litovich? C, Feng? Z, . Current trends and outcomes in cellular therapy activity in the United States, including prospective patient-reported outcomes data collection in the Center for International Blood and Marrow Transplant Research Registry.? Transplant Cell Ther. 2024;30(9):917.e1-917.e12. doi:10.1016\/j.jtct.2024.06.021","DOI":"10.1016\/j.jtct.2024.06.021"},{"key":"coi250067r7","unstructured":"Center for International Blood and Marrow Transplant Research. Accessed September 6, 2023. https:\/\/cibmtr.org\/CIBMTR\/Resources\/Publicly-Available-Datasets"},{"key":"coi250067r14","doi-asserted-by":"crossref","unstructured":"Mehta? RS, Petersdorf? EW, Wang? T, Lee? SJ. Haploidentical versus mismatched unrelated donor hematopoietic cell transplantation: HLA factors and donor age considerations.? Transplant Cell Ther. 2024;30(9):909.e1-909.e11. doi:10.1016\/j.jtct.2024.07.005","DOI":"10.1016\/j.jtct.2024.07.005"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2840877\/jamaoncology_mehta_2025_oi_250067_1767385913.58702.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T16:01:11Z","timestamp":1768492871000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2840877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2025.4551","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}