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.