Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide.
Abstract
<h4>Purpose</h4>Increasing the number of hematopoietic stem and progenitor cells within
an umbilical cord blood (UCB) graft shortens the time to hematopoietic recovery after
UCB transplantation. In this study, we assessed the safety and efficacy of a UCB graft
that was expanded ex vivo in the presence of nicotinamide and transplanted after myeloablative
conditioning as a stand-alone hematopoietic stem-cell graft.<h4>Methods</h4>Thirty-six
patients with hematologic malignancies underwent transplantation at 11 sites.<h4>Results</h4>The
cumulative incidence of neutrophil engraftment at day 42 was 94%. Two patients experienced
secondary graft failure attributable to viral infections. Hematopoietic recovery was
compared with that observed in recipients of standard UCB transplantation as reported
to the Center for International Blood and Marrow Transplant Research (n = 146). The
median time to neutrophil recovery was 11.5 days (95% CI, 9 to 14 days) for recipients
of nicotinamide-expanded UCB and 21 days (95% CI, 20 to 23 days) for the comparator
( P < .001). The median time to platelet recovery was 34 days (95% CI, 32 to 42 days)
and 46 days (95% CI, 42 to 50 days) for the expanded and the comparator cohorts, respectively
( P < .001). The cumulative incidence of grade 2 to 4 acute graft-versus-host disease
(GVHD) at day 100 was 44%, and grade 3 and 4 acute GVHD at day 100 was 11%. The cumulative
incidence at 2 years of all chronic GVHD was 40%, and moderate/severe chronic GVHD
was 10%. The 2-year cumulative incidences of nonrelapse mortality and relapse were
24% and 33%, respectively. The 2-year probabilities of overall and disease-free survival
were 51% and 43%, respectively.<h4>Conclusion</h4>UCB expanded ex vivo with nicotinamide
shortens median neutrophil recovery by 9.5 days (95% CI, 7 to 12 days) and median
platelet recovery by 12 days (95% CI, 3 to 16.5 days). This trial establishes feasibility,
safety, and efficacy of an ex vivo expanded UCB unit as a stand-alone graft.
Type
Journal articleSubject
NeutrophilsFetal Blood
Humans
Hematologic Neoplasms
Graft vs Host Disease
Niacinamide
Disease-Free Survival
Transplantation Conditioning
Cord Blood Stem Cell Transplantation
Graft Survival
Adolescent
Adult
Middle Aged
Female
Male
Young Adult
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https://hdl.handle.net/10161/24579Published Version (Please cite this version)
10.1200/jco.18.00053Publication Info
Horwitz, Mitchell E; Wease, Stephen; Blackwell, Beth; Valcarcel, David; Frassoni,
Francesco; Boelens, Jaap Jan; ... Sanz, Guillermo (2019). Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded
Ex Vivo With Nicotinamide. Journal of clinical oncology : official journal of the American Society of Clinical
Oncology, 37(5). pp. 367-374. 10.1200/jco.18.00053. Retrieved from https://hdl.handle.net/10161/24579.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Mitchell Eric Horwitz
Professor of Medicine
Allogeneic stem cell transplantation with a focus on the use of umbilical cord blood
grafts; Allogenic stem cell transplantation for Sickle Cell Disease; Prevention of
acute and chronic graft versus host disease; Improving immune recovery following alternative
donor stem cell transplantation using donor graft manipulation.
Joanne Kurtzberg
Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology,
pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation,
and novel applications of cord blood and birthing tissues in the emerging fields of
cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director
of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant
and Cellular Therapy Program, Director of the Carolina
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