title: MHC Class I Chain-Related Gene A (MICA) Donor-Recipient Mismatches and MICA-129 Polymorphism in Unrelated Donor Hematopoietic Cell Transplantations Has No Impact on Outcomes in Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome: A Center for International Blood and Marrow Transplant Research Study.
abstract: Single-center studies have previously reported associations of MHC Class I Chain-Related Gene A (MICA) polymorphisms and donor-recipient MICA mismatching with graft-versus-host disease (GVHD) after unrelated donor hematopoietic cell transplantation (HCT). In this study, we investigated the association of MICA polymorphism (MICA-129, MM versus MV versus VV) and MICA mismatches after HCT with 10/10 HLA-matched (n = 552) or 9/10 (n = 161) unrelated donors. Included were adult patients with a first unrelated bone marrow or peripheral blood HCT for acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndrome that were reported to the Center for International Blood and Marrow Transplant Research between 1999 and 2011. Our results showed that neither MICA mismatch nor MICA-129 polymorphism were associated with any transplantation outcome (P < .01), with the exception of a higher relapse in recipients of MICA-mismatched HLA 10/10 donors (hazard ratio [HR], 1.7; P = .003). There was a suggestion of association between MICA mismatches and a higher risk of acute GVHD grades II to IV (HR, 1.4; P = .013) There were no significant interactions between MICA mismatches and HLA matching (9/10 versus 10/10). In conclusion, the findings in this cohort did not confirm prior studies reporting that MICA polymorphism and MICA mismatches were associated with HCT outcomes.
authors.affiliation: Department of Pathology, Baylor University Medical Center, Dallas, Texas. Electronic address: medhat.askar@baylorhealth.edu.
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sobecks
authors.affiliation: Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Mike
authors.initials: M
authors.lastname: Haagenson
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Navneet
authors.initials: N
authors.lastname: Majhail
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Abeer
authors.initials: A
authors.lastname: Madbouly
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Dawn
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Aiwen
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Institute of Cellular Experimental Therapy, University Hospital, Essen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
authors.affiliation: Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center-Adults, New York, New York.
authors.forename: Katharine
authors.initials: K
authors.lastname: Hsu
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Pediatrics, University of Minnesota Medical Center, Minneapolis, Minnesota.
authors.forename: Michael
authors.initials: M
authors.lastname: Verneris
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.affiliation: Department of Pathology, Stanford School of Medicine, Palo Alto, California.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernández-Viña
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D011110:Polymorphism, Genetic / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A
keywords: HLA-B mismatch; MICA mismatch; MICA-129 polymorphism