Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014)

Abstract

Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P = .0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P = .06) or graft failure (9% versus 3%; P = .01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio, .09; 95% confidence interval, .01 to .76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.

Keywords: Aspergillosis; Children; Introduction; Race; Survival; Umbilical cord blood transplantation.

Figure 1.. Probability of a) overall survival and b) transplantation-related mortality after umbilical cord blood transplantation by year of transplantation.

The shaded areas correspond to 95% confidence intervals for the overall survival and transplantation-related mortality curves for a given time period. Overall survival (log-rank test; P=0.0002) and transplantation-related mortality (Gray’s test; P=0.001) differed by time period. Specifically, overall survival was lower in 1995–2001 than in either 2002–2007 (P=0.01) or 2008–2014 (P=0.0001). Similarly, transplantation-related mortality was higher in 1995–2001 compared with 2002–2007 (P=0.01) and 2008–2014 (P=0.002). Comparing 2002–2007 and 2008–2014, there were no significant differences in overall survival (P=0.06) and transplantation-related mortality (P=0.36).

Figure 2.. Two-year mortality from invasive fungal infections among children undergoing umbilical cord blood transplantation by year of transplantation.

Mortality from invasive aspergillosis declined during the study period (P<0.0001), while the mortalities from Candida species and non-Aspergillus molds did not differ by year of transplantation.