Title |
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation
|
---|---|
Published in |
Blood, August 2013
|
DOI | 10.1182/blood-2013-05-503177 |
Pubmed ID | |
Authors |
Corey Cutler, Pratik Multani, David Robbins, Haesook T. Kim, Thuy Le, Jonathan Hoggatt, Louis M. Pelus, Caroline Desponts, Yi-Bin Chen, Betsy Rezner, Philippe Armand, John Koreth, Brett Glotzbecker, Vincent T. Ho, Edwin Alyea, Marlisa Isom, Grace Kao, Myriam Armant, Leslie Silberstein, Peirong Hu, Robert J. Soiffer, David T. Scadden, Jerome Ritz, Wolfram Goessling, Trista E. North, John Mendlein, Karen Ballen, Leonard I. Zon, Joseph H. Antin, Daniel D. Shoemaker |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 9 | 64% |
Australia | 2 | 14% |
Japan | 1 | 7% |
Russia | 1 | 7% |
Unknown | 1 | 7% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 11 | 79% |
Scientists | 2 | 14% |
Practitioners (doctors, other healthcare professionals) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 1% |
United Kingdom | 1 | <1% |
Spain | 1 | <1% |
Sweden | 1 | <1% |
Unknown | 193 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 42 | 21% |
Researcher | 39 | 20% |
Student > Master | 19 | 10% |
Student > Bachelor | 16 | 8% |
Student > Doctoral Student | 15 | 8% |
Other | 36 | 18% |
Unknown | 31 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 50 | 25% |
Biochemistry, Genetics and Molecular Biology | 48 | 24% |
Medicine and Dentistry | 28 | 14% |
Immunology and Microbiology | 15 | 8% |
Neuroscience | 4 | 2% |
Other | 19 | 10% |
Unknown | 34 | 17% |