Donor age as a dual‐risk factor for donor safety and recipient survival in allogeneic haematopoietic stem cell transplantation

Donor selection in allogeneic haematopoietic stem cell transplantation (allo-HSCT) requires balancing donor safety and recipient survival. We aimed to identify dual-association donor factors (DADFs)-donor characteristics associated with both increased serious adverse events (SAEs) and inferior patient survival-using umbilical cord blood (UCB) as a donor-safety benchmark. This nationwide retrospective cohort study analysed Japanese registry data (2013-2022) including 22 892 donors and 29 559 recipients. Logistic regression identified donor SAE risk factors, while patient outcomes were evaluated using inverse probability of treatment weighting (IPTW)-adjusted Cox models with UCB as reference. Propensity score matching (PSM) compared UCB with older donor haploidentical transplantation using post-transplant cyclophosphamide (OD-PTCy-Haplo). Among donors, 93 (0.41%) experienced an SAE. Older donor age and female sex were independent risk factors for SAE. In IPTW-adjusted analyses, allo-HSCT from older haploidentical donors was associated with inferior overall survival (OS) and relapse-free survival (RFS) compared with UCB. In PSM analyses of elderly high-risk recipients, OD-PTCy-Haplo resulted in significantly worse OS and RFS than UCB. Older donor age emerged as a donor characteristic associated with increased donor SAE risk and inferior patient survival, particularly in haploidentical transplantation. UCB may offer a more favourable balance between donor safety and patient outcomes in selected high-risk settings.