Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment
| Autor: | John P. Chute, Efrat Landau, Einat Galamidi Cohen, Tony Peled, Cristina Gasparetto, Barbara Waters-Pick, David Snyder, Mitchell E. Horwitz, Joanne Kurtzberg, Gwynn D. Long, Steven Wease, Ashley Morris, Iddo Peleg, Hadas Shoham, Keith M. Sullivan, Dorit Aschengrau, Patrick J. Stiff, Nelson J. Chao, Dima Yackoubov, Etty Friend, David A. Rizzieri, Amnon Peled, Carolyn McDonald |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Niacinamide medicine.medical_specialty Transplantation Conditioning Urology Cord Blood Stem Cell Transplantation Transplantation Chimera Umbilical cord Young Adult fluids and secretions medicine Humans Progenitor cell business.industry Graft Survival General Medicine Middle Aged Fetal Blood Hematopoiesis Transplantation medicine.anatomical_structure Treatment Outcome Hematologic Neoplasms Immunology embryonic structures Bone marrow Stem cell Clinical Medicine business |
| Zdroj: | The Journal of clinical investigation. 124(7) |
| ISSN: | 1558-8238 |
| Popis: | 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 {"type":"clinical-trial","attrs":{"text":"NCT01221857","term_id":"NCT01221857"}}NCT01221857. FUNDING. Gamida Cell Ltd. |
| Databáze: | OpenAIRE |
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