The importance of matching at the human leukocyte antigen (HLA) C locus has not been well defined for unrelated umbilical cord blood transplantation. The selection algorithm for umbilical cord blood units generally considers intermediate resolution HLA typing at A and B, and allele-level at DRB1. We aimed to determine the relative importance of matching at HLA-C in addition to current selection criteria.
We used Cox regression to retrospectively examine for the effect of donor-recipient HLA matching on outcomes of 803 single umbilical cord blood transplantations for leukemia (N=727) and myelodysplastic syndrome (N=76). The primary endpoint was transplant-related mortality. HLA typing was performed using molecular techniques with a minimum of intermediate resolution for HLA-A, -B and -C and allele-level for DRB1.
Compared to transplantations matched at HLA-A, -B, -C, -DRB1 (N=69; HR 1.00), transplant-related mortality risks were higher after transplantations matched at HLA-A, -B, -DRB1 and mismatched at HLA-C (N=23;HR 3.97, 95% CI 1.27 – 12.40, p=0.018). Transplant-related mortality risk were also higher after transplantations with a single mismatch at HLA-A or -B, or -DRB1 and mismatched at HLA-C (N=234; HR 1.70 95% CI 1.06 – 2.74, p=0.029) compared to transplantations matched at HLA-C with a single mismatch at HLA-A, -B, or -DRB1 (N=127; HR 1.00). Examining for an overall effect of HLA disparity on transplant-related mortality, risks were higher with units mismatched at two (N=259; HR 3.27 95% CI 1.42 – 7.54, p=0.006), three (N=253; HR 3.34 95% CI 1.45 – 7.71, p=0.005) or four (N=75; HR 3.51 95% CI 1.44 – 8.58, p=0.006) loci compared to matched units (N=69; HR 1.00).
These data suggest that we re-evaluate the current strategy for umbilical cord blood unit selection, by considering matching at HLA-C for units that are matched at HLA-A, -B, -DRB1 or in the presence of a single locus mismatch at HLA-A, -B or DRB1 to minimize mortality risks.
National Cancer Institute, National Heart Lung and Blood Institute and National Institute for Allergy and Infectious Diseases; Scholar in Clinical Research Award, the Leukemia and Lymphoma Society; Heath Resources and Services Administration; Office of Naval Research, United States Department of Navy; Children’s Leukemia Research Association; INSERM grant TGIR.