title: Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
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.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.forename: Pratik
authors.initials: P
authors.lastname: Multani
authors.forename: David
authors.initials: D
authors.lastname: Robbins
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Thuy
authors.initials: T
authors.lastname: Le
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hoggatt
authors.forename: Louis M
authors.initials: LM
authors.lastname: Pelus
authors.forename: Caroline
authors.initials: C
authors.lastname: Desponts
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.forename: Betsy
authors.initials: B
authors.lastname: Rezner
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.forename: Brett
authors.initials: B
authors.lastname: Glotzbecker
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Edwin
authors.initials: E
authors.lastname: Alyea
authors.forename: Marlisa
authors.initials: M
authors.lastname: Isom
authors.forename: Grace
authors.initials: G
authors.lastname: Kao
authors.forename: Myriam
authors.initials: M
authors.lastname: Armant
authors.forename: Leslie
authors.initials: L
authors.lastname: Silberstein
authors.forename: Peirong
authors.initials: P
authors.lastname: Hu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Wolfram
authors.initials: W
authors.lastname: Goessling
authors.forename: Trista E
authors.initials: TE
authors.lastname: North
authors.forename: John
authors.initials: J
authors.lastname: Mendlein
authors.forename: Karen
authors.initials: K
authors.lastname: Ballen
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Shoemaker
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D015925:Cryopreservation; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D020869:Gene Expression Profiling; D006085:Graft Survival / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D015064:16,16-Dimethylprostaglandin E2