title: HLA Mismatch Is Associated with Worse Outcomes after Unrelated Donor Reduced-Intensity Conditioning Hematopoietic Cell Transplantation: An Analysis from the Center for International Blood and Marrow Transplant Research.
abstract: Over the past 2 decades, reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC HCT) has increased substantially. Many patients do not have fully HLA-matched donors, and the impact of HLA mismatch on RIC HCT has not been examined in large cohorts. We analyzed 2588 recipients of 8/8 HLA-high resolution matched (n = 2025) or single-locus mismatched (n = 563) unrelated donor (URD) RIC HCT from 1999 to 2011. Overall survival (OS) was the primary outcome. Secondary endpoints included treatment-related mortality (TRM), relapse, disease-free survival (DFS), and acute/chronic graft-versus-host disease (GVHD). Adjusted 1- and 3-year OS was better in 8/8- versus 7/8-matched recipients (54.7% versus 48.8%, P = .01, and 37.4% versus 30.9%, P = .005, respectively). In multivariate models 7/8 URD RIC HCT recipients had more grades II to IV acute GVHD (RR = 1.29, P = .0034), higher TRM (RR = 1.52, P < .0001), and lower DFS (RR = 1.12, P = .0015) and OS (RR = 1.25, P = .0001), with no difference in relapse or chronic GVHD. In subgroup analysis, inferior transplant outcomes were noted regardless of the HLA allele mismatched. Previously reported permissive mismatches at HLA-C (C*03:03/C*03:04) and HLA-DP1 (based on T cell-epitope matching) were not associated with better outcomes. Although feasible, single-locus mismatch in RIC URD HCT is associated with inferior outcomes.
authors.affiliation: Department of Pediatric BMT, University of Minnesota, Minneapolis, Minnesota. Electronic address: verneris@umn.edu.
authors.forename: Michael R
authors.initials: MR
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: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Ahn
authors.affiliation: Medical College of Wisconsin, Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Wang
authors.affiliation: National Heart, Lung and Blood Institute, Hematology Branch, Bethesda, Maryland.
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Department of Pathology, Stanford University, Palo Alto, California.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Fernandez-Vina
authors.affiliation: Department of Hematology, Oregon Health and Science University, Portland, Oregon.
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.affiliation: Department of Blood and Marrow Transplantation, University of South Florida, Tampa, Florida.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.affiliation: Department of Hematology/Oncology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Munker
authors.affiliation: Adult HSCT, Pediatric HSCT, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: Medical College of Wisconsin, Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Koreth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality / Q000706:statistics & numerical data*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens
keywords: Bone marrow transplantation; Hematologic malignancies; Leukemia; Pediatric oncology