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

The Journal of clinical investigation, 2014-07, Vol.124 (7), p.3121-3128 [Peer Reviewed Journal]

COPYRIGHT 2014 American Society for Clinical Investigation ;COPYRIGHT 2014 American Society for Clinical Investigation ;Copyright American Society for Clinical Investigation Jul 2014 ;Copyright © 2014, American Society for Clinical Investigation 2014 American Society for Clinical Investigation ;ISSN: 0021-9738 ;EISSN: 1558-8238 ;DOI: 10.1172/JCI74556 ;PMID: 24911148

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Title:
Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment
Author: Horwitz, Mitchell E ; Chao, Nelson J ; Rizzieri, David A ; Long, Gwynn D ; Sullivan, Keith M ; Gasparetto, Cristina ; Chute, John P ; Morris, Ashley ; McDonald, Carolyn ; Waters-Pick, Barbara ; Stiff, Patrick ; Wease, Steven ; Peled, Amnon ; Snyder, David ; Cohen, Einat Galamidi ; Shoham, Hadas ; Landau, Efrat ; Friend, Etty ; Peleg, Iddo ; Aschengrau, Dorit ; Yackoubov, Dima ; Kurtzberg, Joanne ; Peled, Tony
Subjects: Adult ; Blood banks ; Blood platelets ; Bone marrow ; Cells ; Clinical Medicine ; Cord Blood Stem Cell Transplantation - methods ; Expansion ; Fetal blood ; Fetal Blood - cytology ; Fetal Blood - drug effects ; Graft Survival ; Hematologic Neoplasms - blood ; Hematologic Neoplasms - therapy ; Hematopoiesis ; Humans ; Medical research ; Medicine, Experimental ; Middle Aged ; Mortality ; Niacinamide ; Niacinamide - pharmacology ; Patients ; Physiological aspects ; Properties ; Stem cells ; Transplantation ; Transplantation Chimera ; Transplantation Conditioning ; Transplants & implants ; Treatment Outcome ; Young Adult
Is Part Of: The Journal of clinical investigation, 2014-07, Vol.124 (7), p.3121-3128
Description: 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. 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. 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. 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. Clinicaltrials.gov NCT01221857. Gamida Cell Ltd.
Publisher: United States: American Society for Clinical Investigation
Language: English
Identifier: ISSN: 0021-9738
EISSN: 1558-8238
DOI: 10.1172/JCI74556
PMID: 24911148
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
ProQuest Central

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

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