Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation

被引：230

作者：

Cutler, Corey ^{[1
,2
]}

Multani, Pratik ^{[3
]}

Robbins, David ^{[3
]}

Kim, Haesook T. ^{[1
]}

Thuy Le ^{[3
]}

Hoggatt, Jonathan ^{[2
,4
]}

Pelus, Louis M. ^{[5
]}

Desponts, Caroline ^{[3
]}

Chen, Yi-Bin ^{[4
]}

Rezner, Betsy ^{[3
]}

Armand, Philippe ^{[1
]}

Koreth, John ^{[1
]}

Glotzbecker, Brett ^{[1
]}

Ho, Vincent T. ^{[1
]}

Alyea, Edwin ^{[1
]}

Isom, Marlisa ^{[1
]}

Kao, Grace ^{[1
]}

Armant, Myriam ^{[6
]}

Silberstein, Leslie ^{[2
,6
]}

Hu, Peirong ^{[5
]}

Soiffer, Robert J. ^{[1
]}

Scadden, David T. ^{[2
,4
]}

Ritz, Jerome ^{[1
]}

Goessling, Wolfram ^{[1
,2
,7
]}

North, Trista E. ^{[1
,2
,8
]}

Mendlein, John ^{[3
]}

Ballen, Karen ^{[4
]}

Zon, Leonard I. ^{[1
,2
,6
,9
]}

Antin, Joseph H. ^{[1
]}

Shoemaker, Daniel D. ^{[3
]}

机构：

[1] Dana Farber Canc Inst, Boston, MA 02215 USA

[2] Harvard Stem Cell Inst, Cambridge, MA USA

[3] Fate Therapeut, San Diego, CA USA

[4] Massachusetts Gen Hosp, Boston, MA 02114 USA

[5] Indiana Univ, Indianapolis, IN 46204 USA

[6] Childrens Hosp, Boston, MA 02115 USA

[7] Brigham & Womens Hosp, Boston, MA 02115 USA

[8] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[9] Howard Hughes Med Inst, Chevy Chase, MD USA

来源：

BLOOD | 2013年 / 122卷 / 17期

关键词：

UNRELATED DONORS; ACUTE-LEUKEMIA; UNIT PREDOMINANCE; BONE-MARROW; ENGRAFTMENT; ADULTS; RECONSTITUTION; EXPRESSION; RECIPIENTS; EXPANSION;

D O I：

10.1182/blood-2013-05-503177

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 E-2 (dmPGE(2)) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE(2) 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, andmedia) 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 dmPGE(2) before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE(2)-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 dmPGE(2)-treated UCB unit in 10 of 12 treated participants. This study was registered at www.clinicaltrials.gov as #NCT00890500.

引用

页码：3074 / 3081

页数：8

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