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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01221857.
  
  
  BACKGROUND
  Gamida Cell Ltd.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Gwynn D
authors.initials: GD
authors.lastname: Long
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
authors.forename: Ashley
authors.initials: A
authors.lastname: Morris
authors.forename: Carolyn
authors.initials: C
authors.lastname: McDonald
authors.forename: Barbara
authors.initials: B
authors.lastname: Waters-Pick
authors.forename: Patrick
authors.initials: P
authors.lastname: Stiff
authors.forename: Steven
authors.initials: S
authors.lastname: Wease
authors.forename: Amnon
authors.initials: A
authors.lastname: Peled
authors.forename: David
authors.initials: D
authors.lastname: Snyder
authors.forename: Einat Galamidi
authors.initials: EG
authors.lastname: Cohen
authors.forename: Hadas
authors.initials: H
authors.lastname: Shoham
authors.forename: Efrat
authors.initials: E
authors.lastname: Landau
authors.forename: Etty
authors.initials: E
authors.lastname: Friend
authors.forename: Iddo
authors.initials: I
authors.lastname: Peleg
authors.forename: Dorit
authors.initials: D
authors.lastname: Aschengrau
authors.forename: Dima
authors.initials: D
authors.lastname: Yackoubov
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Tony
authors.initials: T
authors.lastname: Peled
mesh_terms: D000328:Adult; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects*; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000097:blood / Q000628:therapy; D006410:Hematopoiesis; D006801:Humans; D008875:Middle Aged; D009536:Niacinamide / Q000494:pharmacology*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009536:Niacinamide