Selection of cord blood unit by CD34 + cell number, CFU-GM number and allele-level HLA matching in single cord blood transplantation

In Japan only single cord blood transplantations (CBTs) are typically performed and their number has increased over 23 years, with ongoing improvement in the results. CBTs with multiple HLA mismatches are usually employed due to a low HLA barrier, and lower engraftment rate is one of problems to overcome. Here, as part of efforts to improve guidelines for the selection and processing of cord blood units for transplantation, we sought to assess the present status of CBTs in Japan, and to elucidate factors contributing to the favorable outcomes, especially focusing on the selection by cell components of cord blood (CB) unit and HLA allele matching. We conducted a nation-wide study analyzing 13,443 patients who underwent first CBT between in Japan between Dec 1997 - Dec 2019 using multivariate regression analysis. Both patient and transplant related variables, such as age and HCT-CI scores, as well as selectable CB unit characteristics were included in the analysis. The interaction analysis elucidated that CB unit selection favoring larger numbers of CD34 cells /kg and CFU-GM number/kg, and not total nucleated cell number/kg contributed to improved engraftment after transplantation. Moreover, a higher CD34+ cell dose was associated with improved overall survival. Distinctive HLA allele matching was observed. 0-1 HLA allele mismatch between patient and donor had favorable engraftment and carried a significantly lower risk of acute GVHD and chronic GVHD, but had a significantly higher leukemia relapse rate, compared with a 3-HLA allele mismatch. HLA-DRB1 mismatches were associated with reduced risk of leukemia relapse. Notably, the number of HLA allele mismatches had no incremental effect on engraftment, acute and chronic GVHD, or relapse incidence. As a result, the 5-year overall survival did not differ significantly between patients receiving CB units with 0-7 HLA allele mismatches. Main points of CB unit selection: First, selection according to a higher number of CD34+/kg and then of CFU-GM/kg is recommended to obtain favorable engraftment. A unit with 0.5 x 10 CD34+/kg is minimally acceptable. For units with a CD34 cell dose of 0.5-1.0 x 10 cells/kg, applying the parameter of ≥20 - 50 x 10 CFU-GM/kg (66.5% of transplanted CB units in this cohort) is associated with a neutrophil engraftment rate of approximately 90%. A unit with ≥1.0 x 10 CD34 /kg can achieve a ≥90% mean neutrophil engraftment rate. Subsequently, HLA allele matching of HLA-A, -B, -C, -DRB1 a