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Clinical implications of HLA locus mismatching in unrelated donor hematopoietic cell transplantation: a meta-analysis

Ruxiu Tie, Tiansong Zhang, Bo Yang, Huarui Fu, Biqing Han, Jian Yu, Yamin Tan and He Huang _

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Oncotarget. 2017; 8:27645-27660. https://doi.org/10.18632/oncotarget.15291

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Abstract

Ruxiu Tie1,*, Tiansong Zhang2,*, Bo Yang3,*, Huarui Fu1, Biqing Han1, Jian Yu1, Yamin Tan1 and He Huang1

1 Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

2 Department of Traditional Chinese Medicine, Jing’an District Central Hospital, Shanghai, China

3 School of Public Health, Wenzhou Medical University, Wenzhou, China

* These authors contributed equally to the work

Correspondence to:

He Huang, email:

Keywords: HLA locus; hematopoietic cell transplantation; unrelated donor; meta-analysis

Received: July 28, 2016 Accepted: January 26, 2017 Published: February 11, 2017

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.


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