Published on July 10, 2026
Reduced Relapse in High Risk Acute Myeloid Leukemia and Myelodysplastic Neoplasms With Permissive HLA-DPB1 Mismatches and Post-Transplant Cyclophosphamide
by Alex Kadhim
Researchers at The University of Texas MD Anderson Cancer Center have demonstrated that permissive human leukocyte antigen (HLA)-DPB1 mismatches can reduce relapse after matched unrelated donor (UD) stem cell transplantation in high-risk AML/MDS when post-transplant cyclophosphamide is used, without increasing graft-versus-host disease (GVHD) or non-relapse mortality (NRM). These findings, published in Leukemia, may have direct implications in donor selection, suggesting DPB1 permissiveness should be considered.
GVHD and NRM remain the major causes of failure after allogeneic stem cell transplantation (allo-SCT) for myeloid malignancies. Previous studies have demonstrated HLA-DPB1 mismatching, especially when classified by T-cell epitope permissiveness, may enhance graft-versus-leukemia effects, but often at the cost of more acute GVHD. As many of these studies predate the routine use of post-transplant cyclophosphamide (PTCy), which has changed GVHD prophylaxis, the authors therefore performed a retrospective analysis of 541 adults. Each patient underwent 8/8 matched unrelated donor allo-SCT from 2011–2024, all receiving tacrolimus, mycophenolate mofetil, and PTCy. Patients were grouped as DPB1 matched (DP-M, n=176), permissive mismatched (DP-P, n=219), non-permissive graft-versus-host direction (DP-NP-GVH, n=82), or non-permissive host-versus-graft direction (DP-NP-HVG, n=64).
In the full cohort, 2-year relapse was lower with DP-P than DP-M (18% vs 28%; HR 0.6, 95% CI 0.4–0.9, p=0.03), while DP-NP-HVG also showed reduced relapse (14%; HR 0.4, 95% CI 0.2–0.9, p=0.02). The key effect was in high-risk AML/MDS (n=192), where DP-P reduced relapse by about half versus DP-M (HR 0.5, 95% CI 0.3–0.8, p=0.01), with 2-year relapse 25% vs 47%. This benefit persisted after adjustment for remission/MRD status (HR 0.50, p=0.01). Overall survival and progression-free survival trended better but were not statistically significant, and DPB1 status did not increase acute or chronic GVHD; grade III–IV acute GVHD was 8% overall, and chronic GVHD was 16%. The study concludes that DPB1-permissive mismatching is a practical donor-selection criterion that may reduce relapse in high-risk AML/MDS in the PTCy era without added GVHD or mortality risk.
Reference:
Smallbone P, Cao K, Saliba RM, et al. Reduced relapse in high risk acute myeloid leukemia and myelodysplastic neoplasms with permissive HLA-DPB1 mismatches and post-transplant cyclophosphamide. Leukemia. 2026;40(5):934-945. http:doi.org/10.1038/s41375-026-02907-4
![]()