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

Abstract

Key Points• Efficacy of transplanting allele-level HLA-matched cord blood units.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 HLAmatched 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. (Blood. 2014;123(1):133-140)

A prospective investigation of cell dose in single-unit umbilical cord blood transplantation for adults with high-risk hematologic malignancies

“…Studies showing a significant impact of HLA match on mortality and/or outcome typically include pediatric patients 7 who receive large units (median of 5 × 10 7 NC/kg in one study). 10 In line with our data, studies restricted to the adolescent and adult patients do not show an association between HLA match and outcome. [25][26][27] Recent data suggests a benefit to HLA allele-level matching, 10 however, analysis of this variable was not possible in our patients, owing to limited allele information of the donor units.…”

“…However, in contrast to previously published data 7,8,10 HLA match (including HLA-C) did not appear to have a significant impact on neutrophil engraftment, OS, PFS or NRM. This may be due to the difference in the size of the graft, patient population treated and a very limited number of patients with 6/6 HLA match.…”

“…7 Preliminary studies suggest HLA-C antigen matching in UCBT may be beneficial in terms of engraftment 8 and transplant-related mortality. 9 Furthermore, allele-level matching has also been described as a potential factor influencing outcome 10 but is not yet a standard practice. Extensive research has been devoted to the use of double cord blood transplantation; however, with higher costs and increased risk of infusion reactions a survival advantage has not yet been demonstrated.…”

Consideration of noninherited maternal Ags as permissible HLA mismatches in cord blood donor selection

“…The importance of matching at HLA-C and allele-level matching for class I and class II HLA in CBT has recently been identified. 2,14 HLA-C was not included in our analyses owing to the lack of maternal and CB HLA-C typing and the absence of HLA-C matching in the BMDW Match algorithm. Similarly, allele-level matching was also not included in our analyses.…”

“…1,2 However, many patients have to accept an HLA-mismatched CB donor because of the poor availability of a 6/6 HLA match (HLA-A and -B at antigenic or intermediate level and -DRB1 at high-resolution level), particularly for patients of ethnicities other than European Caucasoid (EC). 3 This is in spite of the listing of 4600 000 unrelated CB donors on Bone Marrow Donors Worldwide (BMDW).…”