Impact of donor selection in adverse-risk AML undergoing hematopoietic cell transplantation: A study from the EBMT Acute Leukemia Working Party

We evaluated the influence of donor type in 3006 adults with adverse-risk cytogenetic acute myeloid leukemia (AML) in first complete remission undergoing allogeneic hematopoietic cell transplantation (HCT). Donor types included matched sibling (MSD), matched unrelated (MUD), mismatched unrelated (MMUD), and haploidentical donors. At 2 years, leukemia-free survival, overall survival (OS), and graft-versus-host disease (GVHD)-free/relapse-free survival were 47%, 55%, and 36%. Compared with MSD, OS was inferior with MUD (HR 1.36; 95% CI, 1.1–1.67), MMUD (HR 1.4; 95% CI, 1.07–1.83), and haploidentical grafts (HR 1.33; 95% CI, 1.02–1.73). Haploidentical was associated with lower relapse risk (HR 0.72; 95% CI, 0.53–0.97), but higher non-relapse mortality (NRM) (HR 3.85; 95% CI, 2.44–6.08). All alternative donors showed higher rates of grade II–IV acute GVHD. In 702 patients receiving post-transplant cyclophosphamide (PTCy), survival differences attenuated. However, haploidentical and MMUD showed higher risk of grade III–IV acute GVHD (HR 2.61; 95% CI, 1.04–6.54 and HR 3.74; 95% CI, 1.14–12.24), and haploidentical had increased NRM (HR 3.22; 95% CI, 1.23–8.44), without significant relapse. Findings support safety of alternative donors and reinforce MSD as preferred choice in adverse-risk AML. PTCy mitigates but does not eliminate the risk of donor mismatch.