Abstract
PurposeIncreasing 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.MethodsThirty-six patients with hematologic malignancies underwent transplantation at 11 sites.ResultsThe 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.ConclusionUCB 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.
Highlights
Despite remarkable improvement in outcomes of adult recipients of umbilical cord blood (UCB) transplantation, slow hematopoietic recovery continues to be the major limitation of this approach
We show that transplantation of NiCord is safe, is effective in reducing the time to hematopoietic recovery, and does not require coinfusion of a second unmanipulated UCB unit
Ex vivo expansion of UCB stem and progenitor cells has been studied by a number of groups in an attempt to address the important limitation of UCB transplantation.[1,2,4,11,12]
Summary
Despite remarkable improvement in outcomes of adult recipients of umbilical cord blood (UCB) transplantation, slow hematopoietic recovery continues to be the major limitation of this approach. Early-phase, singlecenter studies have demonstrated that ex vivo expansion of UCB stem cells before transplantation has the potential to address this critical shortcoming. By expanding both hematopoietic stem and progenitor cells, the time to neutrophil recovery after myeloablative conditioning can be even more rapid than that after a mobilized peripheral blood stem-cell graft.[1,2,3,4]. On the basis of these results, we conducted a multicenter, phase I/II study of NiCord transplanted as a single, expanded UCB graft after myeloablative conditioning
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