Prostaglandin-modulated Umbilical cord blood hematopoietic stem cell transplantation

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 HuRobert 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

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3074-3081
Number of pages8
JournalBlood
Volume122
Issue number17
DOIs
StatePublished - Oct 24 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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