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

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Summary: 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.

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