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 metaanalysis 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 5 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.

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

“…Most recently, one meta-analysis demonstrated that 9/10 HLA matching had a higher risk of mortality, compared with 10/10 matching, with hazard ratio of 1.27 (95% CI, 1.12 to 1.45; P < .001) [56], which was similar to ours (HR, 1.31; 95% CI, 1.14 to 1.50; P = .001). In addition, the risk for individual HLA allele mismatches was similar with it in our stratified analyses.…”

“…Despite there are several guidelines published, evidence-based recommends have been absent so far [52–55]. Most recently, a published meta-analysis assess the impact of HLA-DPB1 allele mismatches on overall survival of patients receiving unrelated-donor HCT [56]. Other important end points were not mentioned, and many studies with large populations were not included in the review.…”

Alternative donors for allogeneic hematopoietic stem cell transplantation in poor-risk AML in CR1

“…A recent meta-analysis of 7 retrospective studies comparing 10/10 MUD and 9/10 MUD alloHSCT showed a 27% increased risk of mortality for recipients of a 9/10 MUD. 23 Here, a similarly increased risk (25%) was found when comparing 9/10 MUDs with 10/10 MUDs in patients with poor-risk AML in CR1. These results suggest that transplants using 9/10 MUD may be followed by more stringent prevention of GVHD to limit NRM.…”

Unrelated donor choices for allogeneic hematopoietic cell transplantation in Canada: an evaluation of factors influencing donor selection

“…As the number of available sibling donors declines due to smaller family size in recent decades and potential issues related to donor eligibility in older siblings, transplant centers continue to rely heavily on unrelated donors and cord blood units (CBUs). Canadian transplant centers typically prefer allele matching of prospective donors at HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 loci, with the hope of identifying 10 of 10 HLA‐matched donors . While HLA match level between donor/recipient pairs is considered to be the dominant factor in the selection of unrelated donors, the extent to which additional factors such as sex and donor age influence donor choice remains unclear and the impact of patient ethnicity on donor matching in Canada is unknown.…”

“…Canadian transplant centers typically prefer allele matching of prospective donors at HLA-A, -B, -C, -DRB1, and -DQB1 loci, with the hope of identifying 10 of 10 HLA-matched donors. 3 While HLA match level between donor/recipient pairs is considered to be the dominant factor in the selection of unrelated donors, 4 the extent to which additional factors such as sex and donor age influence donor choice remains unclear and the impact of patient ethnicity on donor matching in Canada is unknown. While OneMatch (OM) search specialists can assist in allogeneic search strategies, donor selection is ultimately the responsibility of Canadian transplant centers.…”