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
J Clin Invest. 2014 Jul;124(7):3121-8. doi: 10.1172/JCI74556. Epub 2014 Jun 9.
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.
造血恢复延迟是脐带血（UCB）移植的一个主要缺点。体外扩增的脐带血移植可缩短造血恢复时间，但扩增后的单位能否实现长期、稳定的植入仍有待证实。我们检验了这样一个假设，即一种由在烟酰胺存在下扩增21天的干细胞和未培养的T细胞组分组成的脐带血来源细胞产品（NiCord）能够加速造血恢复并实现长期植入。
在一项I期试验中，11例血液系统恶性肿瘤成人患者接受了清髓性骨髓预处理，随后接受NiCord和第二个未处理的脐带血单位移植。评估了安全性、造血恢复情况和供体植入情况，并与历史对照进行比较。
未观察到因输注NiCord导致的不良事件。8例患者观察到来自NiCord的中性粒细胞和T细胞完全或部分植入，所有患者的NiCord植入情况保持稳定，中位随访时间为21个月。2例患者通过未处理的单位实现了长期植入。与历史对照相比，接受NiCord移植的患者中性粒细胞恢复的中位时间更早（13天对25天，P<0.001）。1年总生存率和无进展生存率分别为82%和73%。
在烟酰胺存在下扩增并与含T细胞组分一起移植的脐带血来源造血干细胞和祖细胞包含短期和长期重建造血的细胞。这些结果证明进一步研究将NiCord作为单一脐带血移植物进行移植是合理的。如果长期安全性得到证实，NiCord有可能扩大脐带血移植的可及性并降低其毒性。
Clinicaltrials.gov NCT01221857。
Gamida Cell Ltd.
