Donor-recipient age difference, not donor age alone, predicts outcomes in allogeneic hematopoietic stem cell transplantation for aplastic anemia.

BACKGROUND: The impact of donor age on outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aplastic anemia (AA) remains poorly defined. The prognostic value of donor-recipient age difference (DRAD) has rarely been explored. OBJECTIVE: To delineate the optimal donor age window and investigate the prognostic significance of the DRAD in AA patients undergoing allo-HSCT. METHODS: This retrospective study included 261 AA patients who received first allo-HSCT between 2018 and 2025. Patients were stratified into four groups based on donor age quartiles (G1: <20 yrs; G2: 20-29 yrs; G3: 29-38 yrs; G4: >38 yrs) and also by DRAD (DRAD1: <-10yrs; DRAD2: -10 to 10yrs; DRAD3: >+10 yrs). Primary endpoints were overall survival (OS), failure-free survival (FFS), and GVHD-free, relapse-free survival (GRFS). RESULTS: Donor age stratification alone did not significantly affect overall transplant outcomes. However, pairwise comparison showed that the G4 had significantly better OS than the G1 (5-year OS: 88.9% vs. 75.8%; P = 0.047). In multivariable Cox regression, donor age was not an independent predictor, but DRAD emerged as a critical factor. Compared with DRAD2 and DRAD3, DRAD1 was associated with significantly inferior neutrophil (P = 0.008) and platelet (P<0.001) engraftment, overall response (P = 0.029), OS (P<0.001), FFS (P<0.001) and GRFS (P=0.001). DRAD3 showed comparable OS, FFS, and GRFS to DRAD2, but had a significantly higher rate of EBV reactivation (74.6% vs. 59.1% and 59.0%, P = 0.040), suggesting that age-matched donor-recipient pairing may confer a favorable prognosis. CONCLUSION: Donor age alone did not independently predict outcomes, whereas DRAD is a more impactful clinical parameter. A much younger donor (DRAD1) predicts poor outcomes, while age-matched donor-recipient pairing (DRAD2) offers the best balance of efficacy and safety. These findings raise the hypothesis that donor-recipient age matching may be preferable to simply pursuing the youngest donor. However, given the single-center nature of this study, external validation in independent cohorts is warranted before routine adoption in clinical practice.