Donor type remains a crucial determinant of survival and complications for adults with high-risk acute myeloid leukaemia (AML) undergoing stem cell transplantation, a major new analysis shows. The study followed 3,006 adults with adverse-risk cytogenetic AML in their first complete remission who underwent allogeneic haematopoietic cell transplantation, comparing outcomes across four donor categories: matched sibling (MSD), matched unrelated (MUD), mismatched unrelated (MMUD) and haploidentical family donors.
At two years, overall survival was 55%, leukaemia-free survival 47%, and GVHD-free/relapse-free survival 36%. Compared with matched sibling donors, overall survival was significantly worse with every alternative donor type. Hazard ratios for death were 1.36 for MUD, 1.40 for MMUD and 1.33 for haploidentical grafts, confirming MSD as the benchmark option when available.
Trade-offs in relapse and treatment-related deaths
The results revealed a complex trade-off between reducing relapse and avoiding treatment-related harm. Haploidentical transplants were associated with a lower risk of relapse, with a hazard ratio of 0.72, suggesting a potent graft-versus-leukaemia effect. However, this apparent advantage was offset by substantially higher non-relapse mortality, with a hazard ratio of 3.85. All three alternative donor groups also showed increased rates of grade II–IV acute graft-versus-host disease (GVHD) compared with matched siblings.
New GVHD prevention narrows but does not close gap
Researchers also examined a subgroup of 702 patients who received post-transplant cyclophosphamide (PTCy), a widely used strategy to prevent GVHD. In this cohort, survival differences between donor types were attenuated, indicating that PTCy can mitigate some of the risks associated with donor mismatch. Nevertheless, haploidentical and mismatched unrelated donors still carried higher risks of severe, grade III–IV acute GVHD, with hazard ratios of 2.61 and 3.74 respectively. Haploidentical grafts also retained an increased risk of non-relapse mortality (HR 3.22), without a significant rise in relapse. Overall, the findings support the safety and growing role of alternative donors in high-risk AML, while reinforcing matched sibling donors as the preferred choice and showing that PTCy reduces, but does not eliminate, the penalties of donor mismatch.
Reference
Villalba M et al. Impact of donor selection in adverse-risk AML undergoing hematopoietic cell transplantation: A study from the EBMT Acute Leukemia Working Party. Bone Marrow Transplantation. 2025; https://doi.org/10.1038/s41409-025-02751-7.
