Age over sibling: Younger unrelated donors provide superior outcomes compared to sibling donors in fully matched HCT in older AML/MDS patients.

Elderly adults represent a substantial proportion of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS); however, preferential selection of matched related donors (MRD) for elderly allogeneic hematopoietic cell (HCT) recipients is challenged by the excellent outcomes of HCT from unrelated matched donors (MUD). In this retrospective multicenter study, we analyzed overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM at 2 and 5 years) of patients aged ≥ 60 years undergoing HCT for AML/MDS between 2014 and 2024, stratified by donor type and donor age. Among 293 patients (median follow-up 21 months), 75% received MUD transplants. Median donor age was 31 years (MUD) versus 61 years (MRD). Grade 3-4 acute GVHD was more frequent in MRD recipients (14% vs 6%). Two- and five-year OS were 58.2% and 46.8%. MUD recipients had superior 2-year OS (62% vs 47%, p = 0.02) and a trend toward improved 5-year OS. Relapse occurred in 31% (MUD) and 36% (MRD), with 85% within 24 months. Two-year NRM was 16%, primarily infection-related. In multivariable analysis (n = 221), donor age < 30 years independently predicted improved OS and reduced early NRM. Younger unrelated donors, particularly < 30 years, were associated with improved survival, supporting prioritization over elderly siblings.