Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients

Authors

Marc Foca
Salih Demirhan
Flor M Munoz
Kristen G Valencia Deray
Claire E Bocchini
Tanvi S Sharma
Gilad Sherman
William J Muller
Taylor Heald-Sargent
Lara Danziger-Isakov
Samantha Blum
Juri Boguniewicz
Samantha Bacon
Tuhina Joseph
Jodi Smith
Monica I Ardura
Yin Su
Gabriela M Maron
Jose Ferrolino
Betsy C Herold

Publication Date

7-1-2024

Journal

Open Forum Infectious Diseases

DOI

10.1093/ofid/ofae353

PMID

38979014

PMCID

PMC11229698

PubMedCentral® Posted Date

7-1-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Pediatrics, Solid Organ Transplantion, Cytomegalovirus (CMV)

Abstract

BACKGROUND: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes.

METHODS: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models.

RESULTS: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (

CONCLUSIONS: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.