Mitchell E. Horwitz , MD 1 , Stephen Wease , MPH 2 , Beth Blackwell , ScD 2 , David Valcarcel , MD, PhD 3 , Francesco Frassoni , MD 4 , Jaap Jan Boelens , MD, PhD 5 , Stefan Nierkens , PhD 5 , Madan Jagasia , MD 6 , John E. Wagner , MD 7 , Jurgen Kuball , MD 5 , Liang Piu Koh , MBBS, MRCP 8 , Navneet S. Majhail , MD 9 , Patrick J. Stiff , MD 10 , Rabi Hanna , MD 9 , William Y.K. Hwang , MBBS 11 , Joanne Kurtzberg , MD 1 , Daniela Cilloni , MD, PhD 12 , Laurence S. Freedman , PhD 13 , Pau Montesinos , MD 14 , Guillermo Sanz , MD, PhD 14
4 December 2018
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.
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.