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

Marco Zecca, Robert Wynn, Jean-Hugues Dalle, Tobias Feuchtinger, Enrikas Vainorius, Thomas M Brundage, Aastha Chandak, Essy Mozaffari, Garrett Nichols, Franco Locatelli

Research output: Contribution to journalArticle

Abstract

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 (AAUC0-16)-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 AAUC0-16 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 AAUC0-16, 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 AAUC0-16 have the potential of reducing mortality in this at-risk patient population.

Original languageEnglish
JournalBone Marrow Transplantation
DOIs
Publication statusE-pub ahead of print - Feb 25 2019

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Viral Load
Adenoviridae
Pediatrics
Mortality
Viremia
Lymphocytes
Standard of Care
Multicenter Studies
Area Under Curve
Observational Studies
Confidence Intervals

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Association between adenovirus viral load and mortality in pediatric allo-HCT recipients : the multinational AdVance study. / Zecca, Marco; Wynn, Robert; Dalle, Jean-Hugues; Feuchtinger, Tobias; Vainorius, Enrikas; Brundage, Thomas M; Chandak, Aastha; Mozaffari, Essy; Nichols, Garrett; Locatelli, Franco.

In: Bone Marrow Transplantation, 25.02.2019.

Research output: Contribution to journalArticle

Zecca, Marco ; Wynn, Robert ; Dalle, Jean-Hugues ; Feuchtinger, Tobias ; Vainorius, Enrikas ; Brundage, Thomas M ; Chandak, Aastha ; Mozaffari, Essy ; Nichols, Garrett ; Locatelli, Franco. / Association between adenovirus viral load and mortality in pediatric allo-HCT recipients : the multinational AdVance study. In: Bone Marrow Transplantation. 2019.
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