Donor-Recipient HLA-Matching of Unrelated Cord Blood (CB) Units At High-Resolution Reveals High Degrees of HLA-Mismatch and Alters Graft Selection

Background: While CB units are traditionally matched to the recipient at HLA-A,B antigens & -DRB1 alleles with up to 2 mismatches permitted, significant associations between intermediate resolution HLA-C matching, & also HLA-A,B,DRB1 allele matching, & CB transplantation (CBT) outcomes have recently been reported. This suggests that CB donor-recipient match criteria should be upgraded to 6 HLA-alleles or higher. However, how to clinically implement higher resolution HLA-matching & its affect upon CB unit selection are unknown. Methods: We analyzed the HLA-match grade of 96 double-unit CB grafts (units 1a & 1b) & the 1-2 back-up units chosen for each transplant at various match grades. 362 CB units were selected for 95 patients (1 patient was transplanted twice) who underwent CBT from 1/2009-6/2012 for hematologic malignancies. Units were selected based on cryopreserved TNC dose (≥ 1.5, later increased to ≥ 2.0 x 10⁷/kg), donor-recipient 4-6/6 HLA-A,B antigen, -DRB1 allele match & CB bank. Unit-unit match was not considered. High-resolution typing was obtained prospectively but usually did not influence unit selection. Results: The median age was 41 years (range 1-69) & the median weight was 65 kgs (range 10-125). The median TNC/kg x 10⁷ of units 1a & 1b (n = 192) was 2.89 (range 1.53-17.78), & their median donor-recipient HLA-match was 4/6 (range 1-6/6), 5/8 (range 2-8/8), & 6/10 (range 2-9/10) at 6, 8 & 10 HLA-alleles, respectively. The median (range) of 6/6 HLA-A,B antigen,-DRB1 allele matched units (n = 9) was 6/6 (3-6/6), 7/8 (5-8/8) & 9/10 (7-9/10) at 6, 8, & 10 allele resolution, respectively. However, 5/6 HLA-A,B antigen, -DRB1 allele matched units (n = 90) were a median (range) of 5/6 (2-5/6), 6/8 (3-7/8) & 7/10 (3-9/10) at allele resolution. Moreover, 4/6 HLA-A,B antigen, -DRB1 allele matched units (n = 93) were a median (range) of 3/6 (1-4/6), 4/8 (2-6/8) & 5/10 (2-8/10) at allele resolution. We then evaluated how often the use of higher resolution HLA-match criteria would change graft selection to substitute one or both back-up units over units 1a &/or 1b, & the effect on the graft TNC dose (Table). If a TNC/kg ≥ 2.0 x 10⁷ & a better HLA-match were required, unit selection would change in 38/96 (40%) of transplants for 10 allele HLA-match. The effect on TNC was minimal (≤ 12% reduction in the total graft TNC dose). Conclusions: Units currently chosen based on HLA-A, B antigen, -DRB1 allele match have a very high degree of mismatch at higher resolution. Adoption of higher match grade criteria will frequently change the selection of the “optimal” graft. While the new lower limit of acceptable HLA-match & how to “trade off” higher resolution match against TNC dose are unknown, our data suggest that higher resolution HLA-match is frequently possible without significant compromise in graft dose.