Work

Impact of Donor Age and Donor-Recipient Sex Mismatch on Hematopoietic Cell Transplantation Outcomes

Year: 2025

Type: article

Abstract: Background Among donor-related factors, younger age is consistently associated with improved hematopoietic cell transplantation (HCT) outcomes. While a female donor for a male recipient (F-to-M) can pose an increased risk of graft-versus-host disease (GVHD), it may also potentially reduce relapse through mismatched minor histocompatibility antigens (H-Y) contributing to the graft-versus-leukemia effect. How to select a donor while considering both these factors (donor age and sex-mismatch) is unclear. Objective To assess the independent and combined effects of donor age (younger, <30 vs. older, ≥30 years) and donor-recipient sex-mismatch (F-to-M vs. others) among patients who underwent 10/10 HLA-matched unrelated donor HCT with calcineurin inhibitor-based prophylaxis. An existing publicly available Center for International Blood and Marrow Transplant Research dataset was used for analysis. Due to multiple testing, a two-sided p-value of <.01 was considered significant for multivariate analysis (MVA) and <.0025 for pairwise analysis. Results Characteristics of 14147 patients studied are shown in [Fig 1] . In MVA, both donor age (≥30 years: HR 1.12, 95% CI 1.07-1.178, P <.001) and sex-mismatch (F-to-M; HR, 1.09, 95% CI 1.02-1.17, P =0.005) were independent predictors of OS. As both factors had similar hazards, it was conceivable that the presence of two favorable factors (younger donor/not F-to-M) would be associated with best outcomes, two unfavorable factors (older donor/ F-to-M) would be associated with the worst outcomes, while the presence of either one of unfavorable and one of the favorable factors would yield comparable intermediate outcomes. This is indeed what was observed: compared to the younger donor/not F-to-M, the older donor/F-to-M had the highest hazards of overall mortality, while the other two groups had a HR of 1.16 and 1.15 [Fig 2] . Similar patterns were noted for non-relapse mortality. The risk of relapse and day 100 grade II-IV acute GVHD did not differ among the groups. The risk of chronic GVHD was significantly higher with older F-to-M donors, among bone marrow recipients. Conclusions Our study suggests that both older donor age and sex-mismatch (F-to-M) are independent negative predictors of OS. However, the effect of F-to-M when assessed by donor age groups was rather negligible. Although it may increase the risk of overall mortality in recipients with younger donor, but not in those with older donors. Selection of a donor incorporating these factors requires further investigation, especially in the era of novel GVHD prophylaxis.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.396