Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy.

Publication Type:

Journal Article

Source:

Blood, Volume 123, Issue 1, p.133-40 (2014)

Keywords:

2014, Center-Authored Paper, Clinical Research Division, November 2013

Abstract:

We studied the effect of allele-level matching at HLA-A, -B, -C and -DRB1 in 1568 single umbilical cord blood (UCB) transplantations for hematologic malignancy. The primary endpoint was non-relapse mortality (NRM). Only 7% of units were allele matched at HLA-A, -B, -C, -DRB1; 15% were mismatched at one, 26% at two, 30% at three, 16% at four and 5% at five alleles. In a subset of cases, allele-level HLA-match was assigned using imputation; concordance between HLA-match assignment and outcome correlation was confirmed between the actual and imputed HLA-match groups. Compared to HLA-matched units, neutrophil recovery was lower with mismatches at three (OR 0.56, p=0.011), four (OR 0.55, p=0.014) or five (OR 0.45, p=0.009) but not one or two alleles. NRM was higher with units mismatched at one- (HR 2.79; 26%), two- (HR 2.69; 26%), three- (HR 3.60; 34%), four- (HR 3.48; 37%) or five-alleles (HR 4.61; 41%) compared to HLA-matched units (9%; p<0.001). The observed effects are independent of cell dose and patient age. These data support allele-level HLA-matching in the selection of single UCB units. Mismatches at one or two alleles are better tolerated than mismatches at three or four alleles and mismatches at five alleles should be avoided.