Clinical Impact of HLA‐DPB1 Permissiveness Models on Acute GVHD and Survival After Unrelated Allogeneic HCT: A Single‐Centre Brazilian Cohort

ABSTRACT

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.