The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) Score for HLA Class I Graft-Versus-Host Disparity Is Associated with Increased Acute Graft-Versus-Host Disease in Haploidentical Transplantation with Post-Transplant Cyclophosphamide

Abstract The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score quantifies the number of PIRCHE between patient and donor pairs and represents an in silico measure of indirect alloreactivity. This biologic process is defined as T cell recognition of epitopes derived from mismatched, allogeneic HLA peptides that are subsequently presented by shared HLA molecules. Its association with clinical outcome has not been examined in haplo-HCT with PTCy. We hypothesized that PIRCHE scores would correlate with indirect alloreactivity and predict graft-versus-host disease (GvHD) risk and incidence of relapse after haplo-HCT with PTCy. To address this, we retrospectively analyzed 148 patients who received peripheral blood, T cell-replete haplo-HCT with PTCy at a single center between 2009 and 2016. PIRCHE scores (PS) were calculated using the PIRCHE online matching tool. PS were categorized by class and vector. The median class I graft-versus-host (GvH) PS was 11 (range, 0-56), while the median class I host-versus-graft (HvG) PS was 10 (range 0-51). The class I GvH PS was associated with increased grade II-IV aGvHD (adjusted HR or aHR 1.03 per PS unit increase; 95% CI 1.01-1.05; p=0.008) but not chronic GvHD or incidence of relapse. PIRCHE scores represent a novel strategy to predict clinical outcome in haplo-HCT. Further studies using registry data and prospective cohorts are warranted to validate these findings.