With the goal of overcoming the significant delay in neutrophil recovery that occurs following transplantation with umbilical cord blood (CB), we have successfully developed a novel and clinically feasible methodology utilizing an engineered Notch ligand for the ex vivo generation of increased numbers of CD34+ cells. A Phase I clinical trial utilizing Notch-mediated expanded CB progenitors in patients undergoing a myeloablative cord blood transplant (CBT) is currently underway. Results from this trial have not only demonstrated the safety of this approach, but more importantly have for the first time demonstrated that rapid myeloid engraftment can be achieved following infusion of ex vivo expanded hematopoietic progenitors. A significant reduction in median time to an absolute neutrophil count of 500/

Public Health Relevance

Patients undergoing a cord blood transplant, who are often of minority or mixed ethnicity background, are at increased risk of infection and early death following the transplant due to the significant delay in white blood cells recovery (in particular, neutrophils) that these patients experience. However, using a novel culture methodology, we have demonstrated for the first time the ability to generate increased numbers of cells from a single unit of cord blood that are capable of rapid neutrophil recovery when infused in the clinical setting. Further development of this product to confirm our initial promising results requires additional clinical trials that, if successful, could change the way cord blood transplantation is performed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
High Impact Research and Research Infrastructure Programs (RC2)
Project #
5RC2HL101844-02
Application #
7939787
Study Section
Special Emphasis Panel (ZHL1-CSR-H (O2))
Program Officer
Mondoro, Traci
Project Start
2009-09-30
Project End
2013-06-30
Budget Start
2010-09-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$1,732,054
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Milano, Filippo; Gooley, Ted; Wood, Brent et al. (2016) Cord-Blood Transplantation in Patients with Minimal Residual Disease. N Engl J Med 375:944-53
Salit, Rachel B; Milano, Filippo; Delaney, Colleen (2016) Outcomes of Cord Blood Transplantation as Salvage Therapy after Graft Failure or Relapse after Prior Allogeneic Transplantation. Biol Blood Marrow Transplant 22:339-343
Milano, Filippo; Chien, Jason W; Riffkin, Ivy et al. (2012) Stable long-term pulmonary function after myeloablative double cord blood transplant. Biol Blood Marrow Transplant 18:309-13
Milano, Filippo; Pergam, Steven A; Xie, Hu et al. (2011) Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients. Blood 118:5689-96
Dahlberg, Ann; Delaney, Colleen; Bernstein, Irwin D (2011) Ex vivo expansion of human hematopoietic stem and progenitor cells. Blood 117:6083-90