Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment Journal Article


Authors: Horwitz, M. E.; Chao, N. J.; Rizzieri, D. A.; Long, G. D.; Sullivan, K. M.; Gasparetto, C.; Chute, J. P.; Morris, A.; McDonald, C.; Waters-Pick, B.; Stiff, P; Wease, S; Peled, A; Snyder, D.; Cohen, E. G.; Shoham, H.; Landau, E.; Friend, E.; Peleg, I.; Aschengrau, D.; Yackoubov, D.; Kurtzberg, J; Peled, T.
Article Title: Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment
Abstract: 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 long-term engraftment. 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%, respectively. 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 transplantation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01221857. FUNDING: Gamida Cell Ltd.
Journal Title: The Journal of clinical investigation
Volume: 124
Issue: 7
ISSN: 1558-8238; 0021-9738
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 3121
End Page: 3128
Language: eng
DOI/URL:
Notes: LR: 20150902; ClinicalTrials.gov/NCT01221857; GR: P01-CA047741-19/CA/NCI NIH HHS/United States; GR: P30 CA014236/CA/NCI NIH HHS/United States; JID: 7802877; 25X51I8RD4 (Niacinamide); OID: NLM: PMC4071379; 2014/01/07 [received]; 2014/04/17 [accepted]; 2014/06/09 [aheadofprint]; 2014/06/09 [epublish]; ppublish