Prostaglandin-modulated Umbilical cord blood hematopoietic stem cell transplantation

Abstract

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates, and early mortality. 16,16-Dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE2 could improve patient outcomes by increasing the "effective dose"ofHSCs. Molecular profiling approaches were usedtodetermine the optimalexvivo modulation conditions (temperature, time, concentration, and media) for useinthe clinical setting.A phase1 trial was performedtoevaluate the safety and therapeutic potentialofex vivo modulationofa single UCB unit using dmPGE2 before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE2-treated UCB units. We observed encouraging trends in efficacy, with accelerated neutrophil recovery (17.5 vs 21 days, P 5.045), coupled with preferential, long-term engraftment of the dmPGE2-treated UCB unit in 10 of 12 treated participants. This study was registered at www. clinicaltrials.gov as #NCT00890500. © 2013 by The American Society of Hematology.