Cord Blood (CB) Bank Log CD34⁺ and CD34⁺ Subsets (CD38⁻, CD61⁺, CD90⁺) Are Significantly Correlated to Log Total CFU, CFU-GEMM, CFU-GM and BFU-E: A Report from the COBLT Program.

We and others have previously demonstrated that unrelated cyropreserved banked CB is an effective alternative source of allogeneic stem cells but is limited by delays in myeloid and platelet engraftment and immune reconstitution (Kurtzberg et al, NEJM 1996; Cairo et al, Blood 1997). CB nucleated (nuc) cell count, nucleated RBC and total CFU have been previously demonstrated to be associated with time to hematopoietic reconstitution (Rubinstein et al, NEJM 1998; Stevens et al, Blood 2002). More recently CB CD34⁺ content has been demonstrated to be significantly correlated to speed of engraftment and survival (Wagner et al, Blood 2002; Styczynski et al, BMT 2004). CB CD34⁺ subsets (CD38⁻, CD61⁺, CD90⁺) may also be critically important in predicting time to CB hematopoietic reconstitution, ex-vivo CB expansion and/or CB gene therapy. We investigated the relationships of CB CD34⁺ and CD34⁺ subsets with CB total CFU, CFU subsets, nuc cell, nuc RBC, ethnicity, gender, birth weight (BWT), gestational age (GA) and type of delivery in over 8,000 CB units. Briefly, CB was collected and processed (Fraser et al, J Hematother 1998) and aliquots were obtained for flow cytometry and in-vitro colony assays. Statistical analysis was based on multiple regression analysis and analysis or variance of logged counts. Approximately 35,000 maternal donors were screened, 20,700 consented, 16,700 CB collected and 8,730 CB units entered long-term cryopreserved storage. Ethnic distribution was 42% Caucasian, 21% Hispanic, 14% African-American, 11% Asian and 12% mixed. CB was collected by vaginal delivery (74%), at 39–40 weeks GA (61%) and 3–4000 Gm BWT (73%). Mean ± SD CD34⁺ and CD34⁺/38⁻, 61⁺, 90⁺ were 34±42, 3.4±4.8, 7.3±9.5 and 0.3±1.9 x 10⁵, respectively. Mean SD of total CFU, BFU-E, CFU-GM and CFU-GEMM was 23.2±19.8, 13.3±3.1, 9.3±8.6 and 0.5±1.1, respectively. There was a significant correlation of log CD34⁺ with log nuc cell count and log nuc RBC count (R= 0.64, p<0.001 and R= 0.56, p<0.001). There was significant correlation of log CD34⁺ with log total CFU (R= 0.67, p<0.001), CFU-GM (R= 0.68, p<0.001), BFU-E (R= 0.61, p<0.001) and CFU-GEMM (R=0.52, p<0.001). Furthermore there was a significant correlation of log CD34 subsets (CD38⁻, CD61⁺, CD90⁺) with log total CFU and CFU subsets (R 0.26–0.55, p<0.001). Lastly, there was a significant increase in CD34⁺/CD38^- and CD34⁺/CD61⁺ in Caucasians and Hispanics (p<0.001), a direct and inverse correlation with BWT and GA, respectively (p<0.001) and significant increase in CD34⁺/CD61⁺ in males (<0.035). In summary, post processing CB CD34⁺ and CD34⁺ subsets are significantly correlated to nuc cell, nuc RBC and in-vitro CFU and may potentially correlate with the kinetics and quality of lineage specific hematopoietic reconstitution following UCBT and that ethnicity, gender, BWT and GA may be important in CB unit selection in the future. [This research was supported by NHLBI (N01-HB-67136, HB-67142, HB-67132 and HB-67141)].