CHIME: a novel HLA eplet model associates with non-relapse mortality in haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

The importance of HLA mismatch in haploidentical hematopoietic cell transplantation (HaploHCT) with post-transplant cyclophosphamide (PTCy) is debated. If HLA mismatch does impact outcomes, a molecular mismatch model could predict transplant outcomes more effectively than allele mismatch. In this retrospective study, we quantified molecular HLA disparity using eplet mismatch for 265 patient-donor pairs undergoing HaploHCT with PTCy for hematologic malignancy. We discovered an interaction among eplet mismatch (EpMM), HLA class, and mismatch vector that was associated with clinical outcomes. This interaction was termed Class-wise HLA Imbalance of Mismatched Eplets (CHIME), which comprised risk scores of 0, 1, and 2. The CHIME score retained association with non-relapse mortality (CHIME 1 vs. 0, HR 2.85 (1.10-7.37); CHIME 2 vs. 0, HR 3.63 (1.36-9.68), adjusted p = 0.046) and severe aGvHD grade III-IV (CHIME 1 HR 7.82 (1.03-59.22); CHIME 2 HR 8.08 (1.01-64.63), adjusted p = 0.046) after adjustment for transplant-related variables. The CHIME score, when combined with CD3 cell dose, correlated with higher rates of cytokine release syndrome (CRS). The CHIME model may improve clinical outcome prediction over HLA antigen or allele mismatch.