Association between adenovirus viral load and mortality in pediatric allo-HCT recipients: the multinational AdVance study.

This multivariable analysis from the AdVance multicenter observational study assessed adenovirus (AdV) viremia peak, duration, and overall AdV viral burden-measured as time-averaged area under the viremia curve over 16 weeks (AAUC)-as predictors of all-cause mortality in pediatric allo-HCT recipients with AdV viremia. In the 6 months following allo-HCT, 241 patients had AdV viremia ≥ 1000 copies/ml. Among these, 18% (43/241) died within 6 months of first AdV ≥ 1000 copies/ml. Measures of AdV viral peak, duration, and overall burden of infection consistently correlate with all-cause mortality. In multivariable analyses, controlling for lymphocyte recovery, patients with AdV AAUC in the highest quartile had a hazard ratio of 11.1 versus the lowest quartile (confidence interval 5.3-23.6); for peak AdV viremia, the hazard ratio was 2.2 for the highest versus lowest quartile. Both the peak level and duration of AdV viremia were correlated with short-term mortality, independent of other known risk factors for AdV-related mortality, such as lymphocyte recovery. AdV AAUC, which assesses both peak and duration of AdV viremia, is highly correlated with mortality under the current standard of care. New therapeutic agents that decrease AdV AAUC have the potential of reducing mortality in this at-risk patient population.