Protective Effect of HLA-DPB1 Mismatch Remains Valid in Reduced-Intensity Conditioning Unrelated Donor Hematopoietic Cell Transplantation

A mismatch at HLA-DPB1 locus is associated with higher acute GVHD and lower relapse rate after myeloablative (MAC) allogeneic hematopoietic cell transplantation (alloHCT). Also, in MAC setting, mismatch permissiveness and expression level impact alloHCT outcomes. However, in reduced intensity (RIC), DP mismatch effect on transplant outcomes is unknown. We retrospectively evaluated DP mismatch influence (number, permissiveness, and expression) on HCT outcomes in 310 patients with high-resolution typing (HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1), who underwent RIC-HCT. By multivariable analysis, 11/12 had better overall survival (OS) and relapse vs. 12/12 (HR=1.61 and 2.02; p=0.04 and 0.01, respectively) and better OS vs. 10/12 (HR=1.68; p=0.02). Within the 11/12, non-permissive mismatch (NoPR) was associated with higher risk of grade II-IV acute GVHD (HR=1.97; p=0.005) and non-relapse mortality (HR=2.13; p=0.02) vs. permissive (PR). Grouping 11/12 based on the DP expression conferred higher mortality (HR=3.78; p= 0.003) when low expressers received a graft from high expressers (AG) vs. low expressers (AA). Better OS was achieved in PR 11/12, when expression was low in patient and donor (AA) vs. all other combinations. Therefore, in RIC HCT, a single DP mismatch has a protective role, especially in permissive setting, when donor and recipient are low expressers.