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Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment
Mitchell E. Horwitz, … , Joanne Kurtzberg, Tony Peled
Mitchell E. Horwitz, … , Joanne Kurtzberg, Tony Peled
Published June 9, 2014
Citation Information: J Clin Invest. 2014;124(7):3121-3128. https://doi.org/10.1172/JCI74556.
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Clinical Medicine Clinical trials

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

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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.

Authors

Mitchell E. Horwitz, Nelson J. Chao, David A. Rizzieri, Gwynn D. Long, Keith M. Sullivan, Cristina Gasparetto, John P. Chute, Ashley Morris, Carolyn McDonald, Barbara Waters-Pick, Patrick Stiff, Steven Wease, Amnon Peled, David Snyder, Einat Galamidi Cohen, Hadas Shoham, Efrat Landau, Etty Friend, Iddo Peleg, Dorit Aschengrau, Dima Yackoubov, Joanne Kurtzberg, Tony Peled

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Figure 3

Hematopoietic recovery following transplantation.

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Hematopoietic recovery following transplantation.
(A) Early white blood ...
(A) Early white blood cell recovery with associated neutrophil engraftment and (B) durability of white blood cell count at late time points in patients transplanted with NiCord and in a historical control cohort. Bars represent the interquartile range. (C) Early platelet recovery and (D) durability of platelet count at late time points in patients transplanted with NiCord and in a historical control cohort. The historical control patients were transplanted with 2 unmanipulated UCB units.
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