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Biol Blood Marrow Transplant. 2019 Sep 26. pii: S1083-8791(19)30635-4. doi: 10.1016/j.bbmt.2019.09.024. [Epub ahead of print]

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-Transplantation Cyclophosphamide.

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BMT and Leukemia Program, Washington University School of Medicine, Saint Louis, Missouri.
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri.
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri. Electronic address:
Division of Hematologic Malignancies and Transplantation, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.


The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score quantifies the number of PIRCHEs in patient-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 haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy). We hypothesized that the PIRCHE score (PS) would correlate with indirect alloreactivity and predict graft-versus-host disease (GVHD) risk and the incidence of relapse after haplo-HCT with PTCy. We retrospectively analyzed 148 patients who underwent peripheral blood stem cell T cell-replete haplo-HCT with PTCy at a single center between 2009 and 2016. For each patient-donor pair, the PS was calculated using the PIRCHE online matching tool. PSs were categorized by class and vector. The median class I graft-versus-host (GVH) PS was 11 (range, 0 to 56), and the median class I host-versus-graft (HVG) PS was 10 (range, 0 to 51). Class I GVH PS was associated with increased risk of grade II-IV acute GVHD (adjusted hazard ratio, 1.03 per PS unit increase; 95% confidence interval, 1.01 to 1.05; P= .008) but not of chronic GVHD or relapse. Our data show that use of the PS is a novel strategy for predicting clinical outcome in haplo-HCT; further studies using registry data and prospective cohorts are warranted to validate these findings.


HLA disparity; Haploidentical hematopoietic cell transplantation; Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score


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