Single-Allele Mismatch May Decrease Non-Relapse Mortality in Unrelated Bone Marrow Transplantation

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A single-allele mismatch was associated with decreased risk of non-relapse mortality and overall mortality compared with a single-antigen mismatch.
A single-allele mismatch was associated with decreased risk of non-relapse mortality and overall mortality compared with a single-antigen mismatch.

Data published in Biology of Blood and Marrow Transplantation reported that a human leukocyte antigen (HLA)-DRB1 single-allele mismatch resulted in a decreased risk of non-relapse mortality (relative risk [RR], 1.33; 95% CI, 1.08-1.63; P =.006) compared with an HLA-DR single-antigen mismatch. A single-allele mismatch also resulted in a decreased risk of non-relapse mortality (RR, 1.25; 95% CI, 1.01-1.57; P =.025) and overall mortality (RR, 1.16; 95% CI, 1.00-1.37; P =.046) compared with an HLA-C single-antigen mismatch.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the curative treatment option for many hematologic cancers. An HLA-identical sibling is the optimal donor but is only available for approximately 30% of patients eligible for allogeneic HCT. High resolution donor-recipient HLA matching has resulted in unrelated bone marrow transplantation (UBMT) with survival rates comparable to those seen in HLA-identical sibling transplants.

Nonetheless, studies have found that a single mismatch at a low resolution antigen level or high resolution allele level in HLA may be associated with increased mortality and decreased rates of survival at 1 year after HSCT.

For the study, researchers collected clinical data from 7608 HSCT recipients in Japan to compare the effect of HLA single-allele and single-antigen mismatched UBMT without in vivo/ex vivo T-cell depletion.

Compared with an HLA-DRB1 single-allele mismatch, patients who received transplants with 1 or more antigen mismatches demonstrated a significant increase in risk of non-relapse mortality (1-antigen/1-allele mismatch: RR, 1.68; 95% CI, 1.03-2.05; P <.001; 2-antigen mismatch: RR, 1.58; 95% CI, 1.04-2.02; P =.001) and overall mortality (1-antigen/1-allele mismatch: RR, 1.27; 95% CI, 1.09-1.47; P =.002; 2-antigen mismatch: RR, 1.27; 95% CI, 1.04-1.57; P =.02).

These results suggested non-relapse mortality was associated with allele or antigen mismatches and with the combined number of mismatches. Rates of 4-year non-relapse mortality were 22% for full match, 27% for single-allele mismatch, 32% for single-antigen mismatch, 31% for 2-allele mismatch, and 38% for 1-antigen/1-allele mismatch.

“Our results support the preference for an allele mismatch rather than an antigen mismatch in UBMT donors,” the authors concluded.

Reference

1. Atsuta Y, Kato S, Morishima Y, et al. Comparison of HLA allele mismatch and antigen mismatch in unrelated bone marrow transplantation in patients with leukemia [published online October 2, 2018]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2018.10.002

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