title: Synergistic effect of major histocompatibility complex class I-related chain a and human leukocyte antigen-DPB1 mismatches in association with acute graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation.
abstract: The clinical relevance of mismatches at the MHC class I-related chain A (MICA) in hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated the association of MICA donor/recipient mismatch and whether there is an interaction between these and HLA-DPB1 mismatch on clinical outcomes after unrelated donor HSCT. Our study included 227 patients who underwent unrelated donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177 (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed using commercially available kits. In univariable analysis, the risk of grade II to IV acute graft-versus-host disease (GVHD) was greater for patients with MICA mismatch (hazard ratio [HR], 1.73; P = .02) than for those with HLA-DPB1 mismatch (HR, 1.62; P = .07). When MICA and HLA-DPB1 were assessed simultaneously, patients mismatched at both loci had the greatest risk (HR, 2.51; P < .01) and those mismatched at only 1 locus had somewhat greater risk (HR, 1.53; P = .12) than patients matched at both loci; this remained significant in multivariable analysis. The 100-day incidence was 66%, 45%, and 31%, respectively (P = .03). Results were similar for grade III and IV acute GVHD, with 100-day incidence 34%, 16%, and 8% (P = .01). These results are clinically pertinent to donor selection strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are at increased risk for acute GVHD.
authors: Allogen Laboratory, Cleveland Clinic, Cleveland, Ohio. Electronic address: askarm@ccf.org.
authors: Medhat
authors: M
authors: Askar
authors: Medical University of the Americas, Charlestown, Nevis.
authors: Yuchu
authors: Y
authors: Sun
authors: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
authors: Lisa
authors: L
authors: Rybicki
authors: Allogen Laboratory, Cleveland Clinic, Cleveland, Ohio.
authors: Aiwen
authors: A
authors: Zhang
authors: Allogen Laboratory, Cleveland Clinic, Cleveland, Ohio.
authors: Dawn
authors: D
authors: Thomas
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Matt
authors: M
authors: Kalaycio
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Brad
authors: B
authors: Pohlman
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Robert
authors: R
authors: Dean
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Hien
authors: H
authors: Duong
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Rabi
authors: R
authors: Hanna
authors: Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, Ohio.
authors: Jaroslaw
authors: J
authors: Maciejewski
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Navneet S
authors: NS
authors: Majhail
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Brian
authors: B
authors: Bolwell
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Ronald
authors: R
authors: Sobecks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004357:Drug Synergism; D005260:Female; D005838:Genotype; D059868:HLA-DP beta-Chains / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen
keywords: Acute graft-versus-host disease; HLA-DP; Hematopoietic stem cell transplantation; MHC class I–related chain A; Mismatch