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Unrelated Donor Age and Recipient Outcomes After Posttransplant Cyclophosphamide vs. Conventional Prophylaxis

Researchers using data from the Center for International Blood and Marrow Transplant Research have found that the long-recognized negative effect of older unrelated donor age on survival after allogeneic hematopoietic cell transplantation appears markedly reduced when posttransplant cyclophosphamide (PTCy) is used for graft-versus-host disease prophylaxis. The study, published in JAMA Oncology, examined more than ten thousand transplants and showed that the detrimental survival association seen with older donors under conventional calcineurin inhibitor (CNI)–based prophylaxis was not statistically significant in patients receiving PTCy. These findings suggest that donor age, historically a major constraint in donor selection, may be less limiting when PTCy is adopted.

Allogeneic transplantation has traditionally favored younger unrelated donors because numerous studies have shown worse outcomes, particularly higher nonrelapse mortality, when donor age increases. This paradigm, however, predates the widespread use of PTCy, which has transformed GVHD prevention and is increasingly used across transplant centers. Whether donor age still matters to the same extent in the PTCy era has been unclear. In this multicenter cohort study, the investigators analyzed registry data from 2017 to 2021 for adults with acute leukemia or myelodysplastic syndrome who received either fully matched (8/8) or mismatched (7/8) unrelated donor grafts. Using an extensive statistical strategy that included LASSO-penalized Cox models, inverse probability of treatment weighting, and XGBoost machine learning, they assessed whether donor age had differential effects on overall survival across prophylaxis strategies.

Among 10,025 patients (mean age 56.5 years), increasing donor age was consistently associated with worse overall survival in the CNI groups, with hazard ratios ranging from 1.004 to 1.009 per year in matched donors and 1.022 to 1.034 in mismatched donors. In contrast, the PTCy cohort showed no meaningful association, with hazard ratios between 1.001 and 1.007, and results were robust across all analytic approaches. The attenuation was driven mainly by the absence of a link between donor age and nonrelapse mortality in the PTCy setting. These findings suggest that PTCy may counteract adverse biological mechanisms associated with older donors, potentially allowing transplant teams to consider a broader pool of unrelated donors and increasing access to timely transplantation.

Reference:

Mehta RS, Sparapani RA, Kanakry CG, et al. Unrelated Donor Age and Recipient Outcomes After Posttransplant Cyclophosphamide vs Conventional Prophylaxis. JAMA Oncol. Published online November 6, 2025.

http://doi.org/10.1001/jamaoncol.2025.4551