Mitchell E. Horwitz
An ex vivo-expanded umbilical cord blood unit appeared safe and effective as a standalone hematopoietic stem cell graft, shortening time to neutrophil and platelet recovery, according to results of a phase 2 study published in Journal of Clinical Oncology.
“The use of dual umbilical cord blood (UCB) grafts has vastly expanded the accessibility of UCB transplantation to adult patients who lack an adequately sized single UCB graft,” Mitchell E. Horwitz, MD, professor of medicine at Duke University School of Medicine, and colleagues wrote. “However, the problem of delayed hematopoietic recovery was not addressed by this technique.”
In this study, researchers evaluated NiCord (Gamida Cell), a UCB graft expanded ex vivo in the presence of nicotinamide and cryopreserved, as a standalone graft transplanted after myeloablative conditioning.
Researchers analyzed 36 patients (median age, 44 years; 55.6% men) with high-risk hematologic malignancies who underwent NiCord transplantation at 11 different sites in the U.S., compared with 146 patients who received standard UCB transplantation with data reported to the Center for International Blood and Marrow Transplant Research.
Results showed the cumulative incidence of neutrophil engraftment of 94% at day 42.
Median time to neutrophil recovery was 11.5 days (95% CI, 9-14) for patients who received NiCord vs. 21 days (95% CI, 20-23) for patients who received standard transplant (P < .001).
Median time to platelet recovery was 34 days (95% CI, 32-42) with NiCord vs. 46 days (95% CI, 42-50) with standard UCB (P < .001).
At day 100, researchers observed cumulative incidence of grade 2 to grade 4 acute graft-versus-host disease of 44% (95% CI, 28-60) with NiCord vs. 56% (95% CI, 47-64) with standard UCB, and incidence of grade 3 and grade 4 acute GVHD of 11% (95% CI, 3-24) vs. 27% (95% CI, 20-34).
Two years after NiCord transplantation, cumulative incidence of all chronic GVHD was 40% (95% CI, 24-57), moderate to severe GVHD was 10% (95% CI, 2-24), nonrelapse mortality was 24% (95% CI, 11-39) and relapse was 33% (95% CI, 16-52).
The unadjusted probability of OS after 2 years was 51% (95% CI, 33-67) and the probability of 2-year DFS was 43% (95% CI, 24-60).
Researchers wrote that the results needed to be considered with some caution because the small sample size of the patients who received NiCord led to wide confidence intervals.
“The study demonstrates the feasibility of an ex vivo-expanded hematopoietic stem cell product manufactured in a centralized cell-processing facility and distributed internationally to three continents,” Horwitz and colleagues wrote. “It is hypothesized that an ongoing prospective, multicenter, phase 3 registration trial comparing [both transplants] will provide confirmation of the findings presented in this study.”
This study was the first to show than an expanded cord blood unit can be infused as a standalone graft that is also capable of providing adequate and lasting hematopoiesis. Rohtesh S. Mehta, MD, assistant professor of stem cell transplantation at The University of Texas MD Anderson Cancer Center, and colleagues wrote in an accompanying editorial.
“The study by Horwitz [and colleagues] is unique because the investigators applied a technology they had originally developed in the double cord blood transfusion setting to expand a single cord blood unit before infusion,” Mehta and colleagues wrote. “This represents an important advance in the field, demonstrating the safety and efficacy of single cord blood transfusion, which will influence future resource use and cord blood banking practices such that smaller units may now be clinically effective.” – by John DeRosier
Disclosures: Horowitz reports honoraria from MacroGenics and MolMed and research funding from Gamida Cell. Please see the study for all other authors’ relevant financial disclosures. Mehta reports no relevant financial disclosures. Please see the editorial for all other author’s relevant financial disclosures.