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

dc.contributor.author

Horwitz, Mitchell E

dc.contributor.author

Chao, Nelson J

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Rizzieri, David A

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Long, Gwynn D

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Sullivan, Keith M

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Gasparetto, Cristina

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Chute, John P

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Morris, Ashley

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McDonald, Carolyn

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Waters-Pick, Barbara

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Stiff, Patrick

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Wease, Steven

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Peled, Amnon

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Snyder, David

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Cohen, Einat Galamidi

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Shoham, Hadas

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Landau, Efrat

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Friend, Etty

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Peleg, Iddo

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Aschengrau, Dorit

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Yackoubov, Dima

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Kurtzberg, Joanne

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Peled, Tony

dc.date.accessioned

2022-03-24T13:18:56Z

dc.date.available

2022-03-24T13:18:56Z

dc.date.issued

2014-07

dc.date.updated

2022-03-24T13:18:55Z

dc.description.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.
dc.identifier

74556

dc.identifier.issn

0021-9738

dc.identifier.issn

1558-8238

dc.identifier.uri

https://hdl.handle.net/10161/24705

dc.language

eng

dc.publisher

American Society for Clinical Investigation

dc.relation.ispartof

The Journal of clinical investigation

dc.relation.isversionof

10.1172/jci74556

dc.subject

Fetal Blood

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Transplantation Chimera

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Humans

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Hematologic Neoplasms

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Niacinamide

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Treatment Outcome

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Transplantation Conditioning

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Cord Blood Stem Cell Transplantation

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Hematopoiesis

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Graft Survival

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Adult

dc.subject

Middle Aged

dc.subject

Young Adult

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Horwitz, Mitchell E|0000-0001-9863-8464

duke.contributor.orcid

Chao, Nelson J|0000-0001-6725-7220

duke.contributor.orcid

Sullivan, Keith M|0000-0002-1379-9216

duke.contributor.orcid

Kurtzberg, Joanne|0000-0002-3370-0703

pubs.begin-page

3121

pubs.end-page

3128

pubs.issue

7

pubs.organisational-group

Duke

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School of Medicine

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Faculty

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Immunology

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Pathology

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Pediatrics

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Duke Cancer Institute

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Global Health Institute

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Initiatives

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Duke Innovation & Entrepreneurship

pubs.organisational-group

Pediatrics, Transplant and Cellular Therapy

pubs.publication-status

Published

pubs.volume

124

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