Current And Future Directions

Delayed engraftment with prolonged neutropenia following UCBT may lead to life-threatening infections. Cell dose has been shown to be critical in predicting the rate of engraftment. Investigators have developed techniques to increase the number of UCB stem cells available for transplantation by ex vivo expansion, with the goal of shortening the period of neutropenia.74-77 These preclinical advances are yet to be translated into improved clinical outcomes. Preliminary results of multidonor, pooled UCB units have been reported in a small series of adult patients.78 TRM is a major complication of allogeneic SCT. Toxicities of the conditioning regimens often limit allogeneic transplantation to younger patients with relatively few comorbidities. In efforts to expand this therapy to older and more frail patients, nonmye-loablative conditioning regimens have been developed. These regimens have been applied in small series of adult UCBTs.79-85 High rates of engraftment (cumulative incidence of 94% with median neu-trophil recovery in 9.5 days), severe GVHD (9%), TRM (28%), and survival (EFS 31% and OS 39%) have been reported.79

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