Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.

Blood 2013 Oct 30;122(17):3074-81. Epub 2013 Aug 30.

Dana-Farber Cancer Institute, Boston, MA;

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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http://dx.doi.org/10.1182/blood-2013-05-503177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811179PMC
October 2013
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References

(Supplied by CrossRef)
Article in New England Journal of Medicine
Gluckman et al.
New England Journal of Medicine 1989
Article in New England Journal of Medicine
Laughlin et al.
New England Journal of Medicine 2001
Article in New England Journal of Medicine
Rocha et al.
New England Journal of Medicine 2004
Article in New England Journal of Medicine
Lessell et al.
New England Journal of Medicine 2001
Article in The lancet oncology
Frassoni et al.
The lancet oncology 2008
Article in Science
Science 2010
Article in Nature medicine
Delaney et al.
Nature medicine 2010
Article in New England Journal of Medicine
New England Journal of Medicine 2012

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