title: Clinical implications of HLA locus mismatching in unrelated donor hematopoietic cell transplantation: a meta-analysis.
abstract: It remains controversial that the impacts of individual HLA locus mismatches on clinical outcomes of patients receiving unrelated-donor hematopoietic cell transplantation (HCT), as compared to HLA allele matched controls. We conducted a meta-analysis to address these issues. Four databases (PubMed, Embase, Web of Science and the Cochrane Library) were searched to select eligible studies. All donor-recipient pairs were high-resolution typing for HLA-A, -B, -C, -DRB1, DQB1 and DPB1 loci. Multivariate-adjusted hazard ratios (HRs) were extracted and pooled using a random-effects model. A total of 36 studies were included, with 100,072 patients receiving HCT. Surprisingly, we found that HLA-DQB1 locus mismatches had no significantly increased risk of multiple outcomes including acute and chronic graft-versus-host disease (GVHD), overall mortality and disease relapse (HR, 1.07; P = .153; HR, 1.07; P = .271; HR, 1.09; P = .230; HR, 1.07; P = .142 and HR, 1.02; P = .806, respectively). Mismatched HLA-DPB1 was significantly associated with a reduced risk of disease relapse (HR, 0.74; P < .001) but not with increased risks of transplant-related mortality (TRM) and overall mortality (HR, 1.09; P = .591; I2 = 74.2% and HR, 1.03; P = .460, respectively). In conclusion, HLA-DQB1 locus mismatches is a permissive mismatching. HLA-DPB1 locus mismatches significantly protect against leukemia relapse. Refining effects of individual HLA locus mismatches contributes to predicting prognosis of patients receiving unrelated donor HCT.
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ruxiu
authors.initials: R
authors.lastname: Tie
authors.affiliation: Department of Traditional Chinese Medicine, Jing'an District Central Hospital, Shanghai, China.
authors.forename: Tiansong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Public Health, Wenzhou Medical University, Wenzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Huarui
authors.initials: H
authors.lastname: Fu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Biqing
authors.initials: B
authors.lastname: Han
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yamin
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D000483:Alleles; D019070:Cell Lineage; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D009026:Mortality; D063868:Patient Outcome Assessment; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D012008:Recurrence; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D006680:HLA Antigens
keywords: HLA locus; hematopoietic cell transplantation; meta-analysis; unrelated donor