Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization

Abstract

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared to historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared to 86 standard UCB recipients at our institution. Median time to neutrophil engraftment was shorter in NiCord than in standard UCB recipients (12.5 days vs. 26 days, p<0.001). Compared to standard UCB transplantation, NiCord recipients had significantly reduced risk for total infection (RR 0.69, p=0.01), grade 2–3 (moderate to severe) infection (RR 0.36, p<0.001), bacterial infection (RR 0.39, p=0.003), and grade 2–3 bacterial infection (RR 0.21, p=0.003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II–IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days compared to standard UCB recipients after adjustment for age and KPS (69.9 days vs. 49.7 days, p=0.005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, reduced total and bacterial infections, and shorter hospitalization in the first 100 days compared to standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit.

Reconstitution of adaptive immunity after umbilical cord blood transplantation: impact on infectious complications

“…This was well demonstrated in a recent study showing that transplantation of ex vivo expanded umbilical cord blood stem cells decreased early infections and hospitalization (85).…”

Functional Integrity and Gene Expression Profiles of Human Cord Blood-Derived Hematopoietic Stem and Progenitor Cells Generated In Vitro

“…In fact, some of these molecules have already been tested in clinical settings or are close to being tested. It is noteworthy that when expanded cells have been taken into the clinic, the results obtained so far have been encouraging [29][30][31][32].…”

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

“…However, there was no significant association between ATG and NRM in this cohort of patients. Further, it is likely that recent techniques of CBT engineering such as ex vivo CBT expansion or CBT fucosylation (to promote CBT homing) are likely to significantly decrease infection-related mortality in CBT recipients in the near future by prompting neutrophil engraftment [31][32][33].…”

“…Two-year incidences of relapse and of NRM were 29% (95% CI, [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and 39% (95% CI, 31-48), respectively. The figures were 25% (95% CI, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and 35% (95% CI, 25-45), respectively, in patients in CR1, versus 36% (95% CI, 22-49, P = 0.06) and 49% (95% CI, 33-62, P = 0.03), respectively, in patients with active disease at transplantation ( Fig. 1).…”

“…Two-year cumulative incidences of chronic and extensive chronic GVHD were 25% (95% CI, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and 12% (95% CI, 7-19), respectively. In multivariate analysis, female recipient (HR = 0.36, 95% CI 0.17-0.78, P = 0.01) and higher TNC infused (HR = 0.69, 95% CI 0.49-0.96, P = 0.03) were each associated with a lower incidence chronic GVHD.…”