Haploidentical versus matched unrelated donor transplantation with post-transplant cyclophosphamide: a platform-dependent machine learning analysis of donor age

作者：Rohtesh S. Mehta, Christopher G. Kanakry, Mariam Nawas, Aleksandr Lazaryan, Jennifer A. Kanakry, Shernan G. Holtan, Taha Al‐Juhaishi, Joseph Rimando, Anurag K. Singh, Jennifer N. Saultz, Shannon R. McCurdy, Filippo Milano · 发表于：Leukemia · 年份：2026 · DOI：10.1038/s41375-026-02903-8 · 被引用次数：1 · 研究领域：Hematopoietic Stem Cell Transplantation、Renal Transplantation Outcomes and Treatments、Acute Lymphoblastic Leukemia research

In allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy), clinicians frequently face a critical choice between a readily available, often younger, haploidentical and a fully matched unrelated donor (MUD). The platform-specific influence of donor age on survival is a critical, unquantified factor that complicates clinical decision-making. We retrospectively analyzed 4258 adult patients with acute leukemia who underwent first allogeneic HCT with PTCy (2017-2021). We employed machine learning (Random Survival Forests and DeepSurv) alongside robust regression models, including Inverse Probability of Treatment Weighting, 1:1 Propensity Score Matching, and Elastic-Net penalized Cox regression. Machine learning models revealed a divergent association of donor age with survival depending on donor type. The MUD-PTCy platform proved remarkably resilient; a 1% absolute increase in mortality risk (equivalent to Number-Needed-to-Harm of 100) did not emerge in donors up to age 50. In stark contrast, the age-sensitive Haploidentical cohort reached this same risk threshold at a donor age of just 38 years. MUD-PTCy was independently associated with a significant overall survival advantage (Adjusted Hazard Ratio 0.85; 95% confidence interval, 0.75-0.97; P = 0.01). This analysis provides a quantitative framework to guide the trade-off between HLA matching and donor age, supporting individualized decision-making and a rationale to reconsider restrictive donor...