title: Predicted Indirectly ReCognizable HLA Epitopes Class I Promote Antileukemia Responses after Cord Blood Transplantation: Indications for a Potential Novel Donor Selection Tool.
abstract: Unrelated cord blood transplantation (UCBT) provides a curative therapy for patients with hematological malignancies. The effect of HLA mismatches in UCBT is currently the subject of debate. HLA-mismatched UCBT may lead to improved leukemia control but also to graft-versus-host disease (GVHD), resulting in nonrelapse mortality (NRM). The aim of this study was to investigate whether indirect recognition of mismatched HLA provides an explanation for the graft-versus-tumor effect and risk of GVHD. The probability of indirect recognition was predicted by the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model. The effect of the numbers of PIRCHE presented on HLA class I and II (PIRCHE-I and -II) was studied in 134 pediatric patients. To study the effects of higher numbers of PIRCHE, patients were divided in 2 equally sized groups, using the median number of PIRCHE as cutoff values. Proportional hazard models and competing risk analyses were performed to study the effect of PIRCHE on the clinical outcomes relapse, acute and chronic GVHD, NRM, and disease-free and overall survival. Above median PIRCHE-I were associated with reduced relapse risk (HR, .26; 95% CI, .07 to .94; P = .04), evaluating the 50 patients transplanted for a malignancy. Both PIRCHE-I and -II were not associated with other clinical outcomes, including GVHD and NRM. These data suggest that high PIRCHE-I may lead to improved graft-versus-tumor effects after UCBT, without an accompanying GVHD risk. Inclusion of PIRCHE in UCB selection criteria may enhance UCBT outcome, which needs to be tested in prospective studies.
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Kirsten A
authors: KA
authors: Thus
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Talitha A
authors: TA
authors: de Hoop
authors: Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Roel A
authors: RA
authors: de Weger
authors: Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Marc B
authors: MB
authors: Bierings
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Jaap Jan
authors: JJ
authors: Boelens
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: e.spierings@umcutrecht.nl.
authors: Eric
authors: E
authors: Spierings
mesh_terms: D000293:Adolescent; D000328:Adult; D001782:Blood Donors; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D046148:Donor Selection / Q000379:methods*; D000939:Epitopes; D005260:Female; D020544:Graft vs Leukemia Effect; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000939:Epitopes; D006680:HLA Antigens
keywords: Donor selection; HLA; Indirect recognition; PIRCHE; Permissible mismatches; UCBT