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Prognostic value of HLA-DQB1 mismatch and donor age in unrelated donor HCT with PTCy

Mehta RS, Aljawai YM, Kebriaei P, et al. The Impact of Isolated HLA-DQB1 Mismatch and Donor Age in Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplant Cyclophosphamide. Transplantation and Cellular Therapy. 2025; (doi: 10.1016/j.jtct.2025.08.011).

Retrospective data suggest concerns typically associated with HLA-DQB1-mismatched donors in hematopoietic cell transplantation (HCT) may not be relevant in the context of post-transplantation cyclophosphamide (PTCy). An isolated HLA-DQB1 mismatch presents in up to 10% of traditional transplants performed with 8/8 allele-level matched unrelated donors (MUD), challenging the clinical utility of this donor profile. To better understand HLA-DQBI mismatch in the modern transplantation landscape, investigators compared outcomes in 988 patients undergoing HCT with PTCy prophylaxis against graft-versus-host disease (GVHD) between 2017 and 2024. Analysis included 854 procedures performed with 10/10 MUD, 47 transplants involving 8/8 MUD with an isolated HLA-DQB1 mismatch, and 87 transplants with 7/8 mismatched unrelated donors (MMUD). Analysis showed that overall survival, progression-free survival, non-relapse mortality, relapse, and chronic GVHD were not significantly different by donor type. The exception was acute GVHD, the risk for which was higher among 7/8 MMUD donors in the grade III-IV category. Risk for aGVHD of grade II-IV severity was elevated in DQB1 mismatch donors, but without statistical significance. While the single-site findings must be validated in larger studies, the results support MUD with isolated HLA-DQB1 mismatch as appropriate for HCT with PTCy. The evidence indicates that older donor age increases risk for grade II-IV acute GVHD, but that this factor does not otherwise predict outcomes.

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