Donor-recipient allele-level HLA matching of unrelated cord blood units reveals high degrees of mismatch and alters graft selection

Abstract

The feasibility of selecting cord blood (CB) units at high-resolution HLA match has not been investigated. We analyzed the high-resolution donor-recipient HLA match of 100 double-unit 4-6/6 HLA-A,-B antigen, -DRB1 allele-matched CB grafts (units 1a and 1b) and their back-up units (n=377 units in total). The median cryopreserved graft dose was 2.9 × 10(7)/kg/unit, and at high resolution these units had a median donor-recipient HLA-allele match of 5/8 (range 2-8/8) and 6/10 (range 2-9/10), respectively. We then evaluated how often use of high-resolution HLA-match criteria would change the original graft selection to substitute one or both of the back-up units for units 1a and/or 1b. On using a model in which both a higher eight-allele HLA match and a cell dose ⩾ 2.0 × 10(7)/kg/unit were required, graft selection changed in 33% of transplants with minimal effect on cell dose (8.3% reduction). In summary, while units chosen based on HLA-A,-B antigen and -DRB1 allele match have substantial mismatch at higher resolution, CB selection based on high-resolution HLA match is possible in a significant proportion of patients without compromise in cell dose.

Figure 1. The distribution of 8 allele donor-recipient HLA-match of 100 double-unit CB grafts (units 1a and 1b, 200 units) originally selected based on 4–6/6 HLA-A,-B antigen, -DRB1 allele match

The majority of CB units (CBU) were either 5/6 or 4/6 at traditional HLA-match grade. At high resolution, 6/6 matched units were at least 5/8 HLA-allele matched, 5/6 units were as low as 3/8 matched, and 4/6 units were as low as 2/8 matched to the recipient.