BACKGROUND. Delayed hematopoietic recovery is a major drawback of
umbilical cord blood (UCB) transplantation. Transplantation of ex vivo–expanded UCB
shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded
unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product
consisting of stem cells expanded for 21 days in the presence of nicotinamide and a
noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide
METHODS. In a phase I trial, 11 adults with hematologic malignancies
received myeloablative bone marrow conditioning followed by transplantation with NiCord
and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment
were assessed and compared with historical controls.
RESULTS. No adverse events were attributable to the infusion of NiCord.
Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in
8 patients, and NiCord engraftment remained stable in all patients, with a median
follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated
unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13
vs. 25 days, P < 0.001) compared with that seen in historical
controls. The 1-year overall and progression-free survival rates were 82% and 73%,
CONCLUSION. UCB-derived hematopoietic stem and progenitor cells expanded
in the presence of nicotinamide and transplanted with a T cell–containing fraction
contain both short-term and long-term repopulating cells. The results justify further
study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed,
NiCord has the potential to broaden accessibility and reduce the toxicity of UCB
TRIAL REGISTRATION. Clinicaltrials.gov NCT01221857.
FUNDING. Gamida Cell Ltd.