Donor age and type in allogeneic haematopoietic stem cell transplantation: Strong effect in MDS, limited in AML

Donor age is an important factor influencing outcomes after allogeneic haematopoietic stem cell transplantation (allo-HSCT), but its relevance across donor types and distinct disease biology in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) remains unclear. We analysed 320 patients with AML/MDS who underwent first allo-HSCT between 2016 and 2024. Donors were categorized as matched or mismatched and further stratified as young (<35 years) or old (≥35 years). Matched donors achieved superior survival compared with mismatched donors, while outcomes with young mismatched donors were intermediate and old mismatched donors were inferior driven by high non-relapse mortality. This effect was most evident in MDS, where young mismatched donors achieved survival similar to matched donors, while old mismatched donors were associated with inferior overall survival (hazard ratio [HR] 2.66) and relapse-free survival (HR 2.45). By contrast, in AML, survival did not differ by donor age; instead, disease biology dominated prognosis, with marrow blasts and European LeukemiaNet (ELN) risk strongly predicting outcomes. In conclusion, donor age interacts with donor type to shape allo-HSCT outcomes, with a marked impact in MDS but limited effect in AML. These findings suggest that old mismatched donors should be avoided in MDS and underscore the importance of disease-specific considerations in donor selection.