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

Abstract

We studied the effect of allele-level matching at human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 in 1568 single umbilical cord blood (UCB) transplantations for hematologic malignancy. The primary end point was nonrelapse mortality (NRM). Only 7% of units were allele matched at HLA-A, -B, -C, and -DRB1; 15% were mismatched at 1, 26% at 2, 30% at 3, 16% at 4, and 5% at 5 alleles. In a subset, 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 with HLA-matched units, neutrophil recovery was lower with mismatches at 3, 4, or 5, but not 1 or 2 alleles. NRM was higher with units mismatched at 1, 2, 3, 4, or 5 alleles compared with HLA-matched units. 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.

Figure 1

Nonrelapse mortality and overall survival. (A) The cumulative incidence of nonrelapse mortality by HLA match: the 3-year incidence of nonrelapse mortality after HLA-matched, 1-allele mismatch, 2-allele mismatch, 3-allele mismatch, 4-allele mismatch, and 5-allele mismatch transplants were 9% (95% CI 4-14), 26% (95% CI 20-32), 26% (95% CI 22-30), 34% (95% CI 30-39), 37% (95% CI 31-43), and 41% (95% CI 30-51), respectively. (B) The probability of overall survival by HLA match: the 3-year probability of overall survival after HLA-matched, 1-allele mismatch, 2-allele mismatch, 3-allele mismatch, 4-allele mismatch, and 5-allele mismatch transplants were 52% (95% CI 42-62), 42% (95% CI 36-49), 47% (95% CI 42-52), 42% (95% CI 37-47), 41% (95% CI 35-47), and 34% (95% CI 23-45), respectively.

Figure 2

Nonrelapse mortality by total nucleated cell dose. (A) The cumulative incidence of nonrelapse mortality by precryopreserved TNC in recipients of 1-allele mismatched transplants: 45% (95% CI 29-62), 24% (95% 13-38), and 21% (14-28) for units with TNC <3 × 10⁷/kg, 3-5 × 10⁷/kg, and >5 × 10⁷/kg, respectively. (B) The cumulative incidence of nonrelapse mortality by precryopreserved TNC in recipients of 2-allele mismatched transplants: 40% (95% CI 27-53), 25% (95% 17-34), and 23% (18-28) for units with TNC <3 × 10⁷/kg, 3-5 × 10⁷/kg, and >5 × 10⁷/kg, respectively. (C) The cumulative incidence of nonrelapse mortality by precryopreserved TNC in recipients of 3-allele mismatched transplants: 52% (95% CI 39-64), 35% (95% 27-42), and 29% (23-35) for units with TNC <3 × 10⁷/kg, 3-5 × 10⁷/kg, and >5 × 10⁷/kg, respectively. (D) The cumulative incidence of nonrelapse mortality by precryopreserved TNC in recipients of 4-allele mismatched transplants: 43% (95% CI 28-58), 39% (95% 30-49), and 29% (21-39) for units with TNC <3 × 10⁷/kg, 3-5 × 10⁷/kg and >5 × 10⁷/kg, respectively.