Clinical Impact of HLA-DPB1 Permissiveness Models on Acute GVHD and Survival After Unrelated Allogeneic HCT: A Single-Centre Brazilian Cohort.
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HLA-DPB1 mismatches are frequent in unrelated allogeneic haematopoietic stem cell transplantation (allo-HCT), even among donor-recipient pairs matched at conventional HLA loci. Models including T-cell epitope (TCE), expression and Predicted Indirectly Recognisable HLA Epitopes (PIRCHE) have been proposed to assess HLA-DPB1 permissiveness. To evaluate the impact of HLA-DPB1 permissiveness assessed by TCE, expression and PIRCHE models on acute graft-versus-host disease (aGVHD) and overall survival after unrelated donor allo-HCT. This retrospective cohort study included 137 recipients who underwent unrelated allo-HCT between 2010 and 2024 at the Bone Marrow Transplant Centre of the Brazilian National Cancer Institute (CEMO-INCA). High-resolution HLA-DPB1 genotyping was performed by next-generation sequencing. HLA-DPB1 permissiveness was evaluated using TCE classification, rs9277534 expression-associated polymorphism and PIRCHE-I/II scores. Multivariable analysis for Grade II-IV aGVHD were performed using the Fine and Grey subdistribution hazards model, and overall survival was assessed using Kaplan-Meier and Cox models. Among 85 donor-recipient pairs initially matched at HLA 10/10, only 20 (23.5%) were also matched at HLA-DPB1. Double HLA-DPB1 GVH-direction mismatches suggested an increased risk of Grade II-IV aGVHD (sHR = 2.82; p = 0.036), as did TCE-1 mismatches (sHR = 3.27; p = 0.041) and the highest PIRCHE-I score tertile (sHR = 3.36; p = 0.052) suggested a borderline association. In HLA 9/10 transplants, a single high-expression GVH-direction mismatch (sHR = 3.33; p = 0.025), as did TCE-1 mismatches (sHR = 3.64; p = 0.015) and the highest PIRCHE-I (sHR = 7.02; p = 0.003), with a similar trend for PIRCHE-II scores tertile suggested association with increased aGVHD risk. None of the HLA-DPB1 permissiveness models or PIRCHE were associated with overall survival. TCE- and PIRCHE-based HLA-DPB1 permissiveness models suggested association with aGVHD risk after unrelated allo-HCT, but given the small size of these subgroups, these findings should be considered hypothesis-generating.