Prostaglandin-modulated Umbilical Cord Blood Hematopoietic Stem Cell Transplantation

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2013 Sep 3

PMID 23996087

Citations 158

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

Affiliations

Soon will be listed here.

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.

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References

Ippoliti A, Isenberg J, Hagie L . Effect of oral and intravenous 16,16-dimethyl prostaglandin E2 in duodenal ulcer and Zollinger-Ellison syndrome patients. Gastroenterology. 1981; 80(1):55-9. View

Avery S, Shi W, Lubin M, Gonzales A, Heller G, Castro-Malaspina H . Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts. Blood. 2010; 117(12):3277-85. PMC: 3069669. DOI: 10.1182/blood-2010-08-300491. View

de Lima M, McNiece I, Robinson S, Munsell M, Eapen M, Horowitz M . Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med. 2012; 367(24):2305-15. PMC: 3805360. DOI: 10.1056/NEJMoa1207285. View

Liu B, Liao C, Chen J, Gu S, Wu S, Xu Z . Significance of increasing adhesion of cord blood hematopoietic cells and a new method: platelet microparticles. Am J Hematol. 2003; 74(3):216-7. DOI: 10.1002/ajh.10412. View

Goessling W, Allen R, Guan X, Jin P, Uchida N, Dovey M . Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell. 2011; 8(4):445-58. PMC: 3148081. DOI: 10.1016/j.stem.2011.02.003. View

Liu H, Rich E, Godley L, Odenike O, Joseph L, Marino S . Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions. Blood. 2011; 118(24):6438-45. PMC: 3236125. DOI: 10.1182/blood-2011-08-372508. View

Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger R, Bernstein I . Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med. 2010; 16(2):232-6. PMC: 2819359. DOI: 10.1038/nm.2080. View

Cutler C, Stevenson K, Kim H, Brown J, McDonough S, Herrera M . Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis. Bone Marrow Transplant. 2010; 46(5):659-67. PMC: 3012740. DOI: 10.1038/bmt.2010.192. View

Ramirez P, Wagner J, DeFor T, Blazar B, Verneris M, Miller J . Factors predicting single-unit predominance after double umbilical cord blood transplantation. Bone Marrow Transplant. 2011; 47(6):799-803. PMC: 3590908. DOI: 10.1038/bmt.2011.184. View

10.

Hoggatt J, Singh P, Sampath J, Pelus L . Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood. 2009; 113(22):5444-55. PMC: 2689046. DOI: 10.1182/blood-2009-01-201335. View

11.

Haspel R, Kao G, Yeap B, Cutler C, Soiffer R, Alyea E . Preinfusion variables predict the predominant unit in the setting of reduced-intensity double cord blood transplantation. Bone Marrow Transplant. 2007; 41(6):523-9. PMC: 2947748. DOI: 10.1038/sj.bmt.1705933. View

12.

Frassoni F, Gualandi F, Podesta M, Raiola A, Ibatici A, Piaggio G . Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study. Lancet Oncol. 2008; 9(9):831-9. DOI: 10.1016/S1470-2045(08)70180-3. View

13.

Wilson D, Quertermus J, Raiser M, Curran J, Robert A . Inhibition of stimulated gastric secretion by an orally administered prostaglandin capsule. A study in normal men. Ann Intern Med. 1976; 84(6):688-91. DOI: 10.7326/0003-4819-84-6-688. View

14.

North T, Goessling W, Walkley C, Lengerke C, Kopani K, Lord A . Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 2007; 447(7147):1007-11. PMC: 2775137. DOI: 10.1038/nature05883. View

15.

Goessling W, North T, Loewer S, Lord A, Lee S, Stoick-Cooper C . Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009; 136(6):1136-47. PMC: 2692708. DOI: 10.1016/j.cell.2009.01.015. View

16.

Barker J, Weisdorf D, DeFor T, Blazar B, McGlave P, Miller J . Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2004; 105(3):1343-7. DOI: 10.1182/blood-2004-07-2717. View

17.

Kim D, Chung Y, Kim T, Kim Y, Oh I . Cotransplantation of third-party mesenchymal stromal cells can alleviate single-donor predominance and increase engraftment from double cord transplantation. Blood. 2003; 103(5):1941-8. DOI: 10.1182/blood-2003-05-1601. View

18.

Foudi N, Gomez I, Benyahia C, Longrois D, Norel X . Prostaglandin E2 receptor subtypes in human blood and vascular cells. Eur J Pharmacol. 2012; 695(1-3):1-6. DOI: 10.1016/j.ejphar.2012.08.009. View

19.

Pelus L, Hoggatt J, Singh P . Pulse exposure of haematopoietic grafts to prostaglandin E2 in vitro facilitates engraftment and recovery. Cell Prolif. 2011; 44 Suppl 1:22-9. PMC: 6372373. DOI: 10.1111/j.1365-2184.2010.00726.x. View

20.

Barker J, Weisdorf D, Wagner J . Creation of a double chimera after the transplantation of umbilical-cord blood from two partially matched unrelated donors. N Engl J Med. 2001; 344(24):1870-1. DOI: 10.1056/NEJM200106143442417. View