Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment.
2014 Jul
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.Galamidi;
Shoham, H.;
Landau, E.;
Friend, E.;
Peleg, I.;
Aschengrau, D.;
Yackoubov, D.;
Kurtzberg, J.;
Peled, T.
Secondary:
J Clin Invest
Volume:
124
Pagination:
3121-8
Issue:
7
PMID:
24911148
DOI:
10.1172/JCI74556
Keywords:
Adult; Cord Blood Stem Cell Transplantation; Fetal Blood; Graft Survival; Hematologic Neoplasms; Hematopoiesis; Humans; Middle Aged; Niacinamide; Transplantation Chimera; Transplantation Conditioning; Treatment Outcome; Young Adult
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.
