title: Impact of HLA-Mismatch in Unrelated Donor Hematopoietic Stem Cell Transplantation: A Meta-Analysis.
abstract: The magnitude of risk associated with 9/10 mismatched unrelated donor (MMURD) hematopoietic stem cell transplantation and that of mismatches at the individual HLA loci remain unclear. We performed a meta-analysis to assess the difference in clinical outcomes between matched unrelated donor (MUD) and MMURD transplantation. A comprehensive search of Medline and Embase for manuscripts regarding transplantation outcomes in primarily adult patients with hematologic malignancies was performed. The pooled effect estimates were calculated using DerSimonian-Laird random effects models. A total of 13 studies were included, reporting on 13,446 transplants. 9/10 MMURD transplantation was associated with worse overall survival compared to 10/10 MUD transplantation (pooled HR: 1.27, 95% CI: 1.12-1.45; n = 7 studies). Mismatch at HLA-A, -B, or -C was associated with significantly worse overall survival compared to MUD transplantation, while there was no significant difference associated with -DQ or -DPB1 mismatch. Inferior survival associated with HLA-DRB1 mismatch could not be ruled out. Data on acute and chronic graft-versus-host disease were scarce but favored MUD transplantation. In summary, this meta-analysis of the available literature favored MUD over MMURD transplantation in hematologic malignancies and further quantifies the risks associated with specific HLA-allele mismatches. Am. J. Hematol. 91:551-555, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Hematology, the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kekre
authors.affiliation: Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Mak
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Konrad H
authors.initials: KH
authors.lastname: Stopsack
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Moritz
authors.initials: M
authors.lastname: Binder
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kazusa
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Elsa
authors.initials: E
authors.lastname: Brånvall
authors.affiliation: Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
mesh_terms: D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens