Background: Adenovirus (AdV) infection is an important cause of mortality among allogeneic hematopoietic cell transplant (allo-HCT) recipients. Current European Conference of Infections in Leukemia (ECIL-4) guidelines support weekly AdV screening for those at-risk and pre-emptive antiviral treatment with off-label cidofovir when adenoviremia is detected. However, there is limited understanding of the relative prognostic strength of different dynamic AdV viral load measures. We examined the association between adenovirus viral load dynamics and mortality in pediatric allo-HCT recipients managed under the current standard of care.
Methods: AdVance was a multinational, multicenter study characterizing the current screening and treatment practices for AdV infection in allo-HCT recipients between January 2013 and September 2015. This analysis focused on pediatric (<18 years) patients who experienced AdV viremia ≥1000 copies/mL within 6 months of HCT. Multivariate Cox Proportional Hazard models, controlling for factors including immune reconstitution, were used to examine the relationship between AdV viral load dynamics (Figure 1) and all-cause mortality in the 6 months after first AdV viremia ≥1000 copies/mL.
Results: 241 pediatric allo-HCT recipients had AdV viremia ≥1000 copies/mL in the 6 months following allo-HCT. Among these, 43/241 (18%) died within 6 months of first AdV ≥1000 copies/mL. AdV viral load dynamics; whether measured by AdV AAUC0-16, peak viremia, 2-week change in viremia, or days of viremia >1000 copies/mL, were consistently correlated with all-cause mortality (Figure 2; hazard ratio [HR] range: 1.3 to 2.3). Most notably, patients with AdV AAUC0-16 in the highest quartile had a HR of 11.6 relative to those in the lowest (confidence interval: 4.7 to 24.0; Figure 3).
Conclusion: AdV infection is a significant risk for allo-HCT recipients. The AdVance study has identified several dynamic measures of AdV viral load that correlate with the risk of mortality in pediatric allo-HCT recipients. Results show for the first time, that AdV AAUC0-16 provides the optimal correlation with mortality in this population and serves as a clinically useful indicator of outcome in patients with AdV infection.
P. Comoli, Chimerix, Inc.: Investigator , Research support .
A. Chandak, Chimerix, Inc.: Research Contractor , Research support . Analytica Laser: Employee , Salary .
E. Vainorius, Chimerix, Inc.: Employee and Shareholder , Salary .
T. Brundage, Chimerix, Inc.: Employee and Shareholder , Salary .
E. Mozaffari, Chimerix, Inc.: Employee and Shareholder , Salary .
G. Nichols, Chimerix, Inc.: Employee and Shareholder , Salary .
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