1. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
- Author
-
Cutler C, Multani P, Robbins D, Kim HT, Le T, Hoggatt J, Pelus LM, Desponts C, Chen YB, Rezner B, Armand P, Koreth J, Glotzbecker B, Ho VT, Alyea E, Isom M, Kao G, Armant M, Silberstein L, Hu P, Soiffer RJ, Scadden DT, Ritz J, Goessling W, North TE, Mendlein J, Ballen K, Zon LI, Antin JH, and Shoemaker DD
- Subjects
- Adult, Aged, Blood Platelets cytology, Blood Platelets immunology, Cells, Cultured, Cryopreservation, Female, Fetal Blood cytology, Fetal Blood immunology, Fetal Blood transplantation, Gene Expression Profiling, Hematologic Neoplasms immunology, Hematologic Neoplasms pathology, Humans, Male, Middle Aged, Transplantation Chimera, Transplantation, Homologous, Treatment Outcome, 16,16-Dimethylprostaglandin E2 pharmacology, Blood Platelets drug effects, Cord Blood Stem Cell Transplantation methods, Fetal Blood drug effects, Graft Survival immunology, Hematologic Neoplasms therapy
- 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" of HSCs. Molecular profiling approaches were used to determine the optimal ex vivo modulation conditions (temperature, time, concentration, and media) for use in the clinical setting. A phase 1 trial was performed to evaluate the safety and therapeutic potential of ex vivo modulation of a 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 = .045), coupled with preferential, long-term engraftment of the dmPGE2-treated UCB unit in 10 of 12 treated participants.
- Published
- 2013
- Full Text
- View/download PDF