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.

Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…This is in line with previous observations from the literature suggesting that increasing HLA mismatch does not have a significant impact on relapse [20,37]. Moreover, our data confirm published studies on association between second field HLA-A, -B, -C, and -DRB1 but not -DQB1 mismatches and poorer outcome of MUD HSCT [6,10,31,32,34,38] and of C*03:03 versus C*03:04 as a permissible mismatch combination in 9/10 MMUD [39]. OS after transplants with a single mismatch in HLA-B or -DRB1 was poorer but did not reach statistical significance because of the small sample size (n = 49 and n = 48, respectively).…”

BSHI guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

“…Although HLA‐DQB1 mismatching did not reach significance in relation to survival, in a German study (Fürst et al., 2013), HLA‐DQ antigen mismatching achieved a higher hazards risk for survival compared with HLA‐DQ antigen matches. A meta‐analysis evaluating data from 36 studies published between 2002 and 2016 concluded that HLA‐DQB1 mismatches were better tolerated than other HLA loci for acute GVHD, supporting previous conclusions (Tie et al., 2017).…”

“…A meta-analysis evaluating data from 36 studies published between 2002 and 2016 concluded that HLA-DQB1 mismatches were better tolerated than other HLA loci for acute GVHD, supporting previous conclusions (Tie et al, 2017).…”

Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation

“…The incidence of grade II to IV aGVHD ranges from 13 to 35% and the incidence of grade III to IV aGVHD is approximately 5.0-7.7% for patients undergoing sibling-identical HSCT [48][49][50][51]. For patients undergoing matched-unrelated donor HSCT, the incidence of grade II-IV aGVHD is between 12.5 and 47.0%, and the incidence of grade III-IV aGVHD is 6.6-13.5% [52][53][54]. For patients who receive haploidentical HSCT, the incidence of grade II-IV aGVHD is between about 18.5 and 43.9%, and the incidence of grade III-IV aGVHD ranges between about 7.9 and 13.8% [55][56][57].…”