Analysis of 402 Cord Blood Units to Assess Factors Influencing Infused Viable CD34+ Cell Dose: The Critical Determinant of Engraftment

Introduction: Criteria for selecting cord blood (CB) units with high engraftment potential are not established. Methods: We investigated the donor variables associated with neutrophil engraftment in recipients of myeloablative double-unit CB transplantation at our transplant center (TC) and then evaluated whether these unit characteristics could be reliably determined at the time of unit selection in 402 CB units thawed at our TC from 10/2005-06/2013. Results: The cumulative incidence of neutrophil engraftment in 130 recipients was 95% (95%CI: 90-98). In multivariate analysis, only the dominant unit infused viable CD34+ cell dose/kg independently influenced engraftment [HR 1.95, p = 0.001] (Figure). We then analyzed the components of infused viable CD34+ cell dose (i.e. post-thaw CD34+ cell count and percent viability) in 402 units (302 domestic and 100 international) from 43 Banks thawed at our TC. Bank CD34+ cell count correlated with post-thaw measurements (r² = 0.6, p < 0.001). The median CD34+ cell recovery was 101% but ranged 12-1480%. Recovery < 65% occurred less frequently in units from FACT-accredited Banks. Moreover, while the median post-thaw CD34+ cell viability was 92%, 33 (8%) units had < 75% viable CD34+ cells post-thaw. Bank FACT accreditation and CB unit cryovolume were significantly associated with post-thaw viability (Table). Bank location (all domestic vs. all international), shipping distance (local vs. distant international) and duration of cryopreservation were not associated with viability. Conclusion: Infused viable CD34+ cell dose was the critical determinant of engraftment, and CD34+ cell count recovery and viability were linked to differences in banking practices. These findings have significant implications for banking and CB unit selection. At our TC, we now prioritize standard 25ml units from FACT-accredited banks and strongly consider the CD34+ cell dose.  However, with such a practice, TC must be able to react to lower than expected post-thaw CD34+ cell counts and/or low CD34+ cell viability. This requires measurement of the infused viable CD34+ cell dose (or another rapidly available measure of potency) on transplant day and a back-up strategy in case of a compromised unit. This is even more critical in single-unit CBT in which engraftment is solely dependent on a single unit.