Cell-free DNA next-generation sequencing successfully detects infectious pathogens in pediatric oncology and hematopoietic stem cell transplant patients at risk for invasive fungal disease.
cell-free DNA
fungal disease
pediatric oncology
pediatric stem cell transplantation
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
02
12
2018
revised:
04
03
2019
accepted:
11
03
2019
pubmed:
4
4
2019
medline:
18
12
2019
entrez:
4
4
2019
Statut:
ppublish
Résumé
We sought to determine if next-generation sequencing (NGS) of microbial cell-free DNA (cfDNA) in plasma would detect pathogens in pediatric patients at risk for invasive fungal disease (IFD). Pediatric hematology, oncology, and stem cell transplant patients deemed at risk for new IFD had blood samples drawn at three time-points separated by 1-month intervals. The primary outcome measure was detection of fungal pathogens compared to standard clinical testing. Secondary outcomes included identification of other infectious pathogens, relationship to European Organization for Research and Treatment of Cancer's Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases' Mycoses Study Group (EORTC/MSG) guidelines, and assessment of antifungal therapy. NGS identified fungal pathogens in seven of 40 at-risk patients for IFD and results were identical in four of six proven cases, including Aspergillus fumigatus by lung biopsy, Candida albicans by blood or pancreatic pseudocyst cultures, and Rhizopus delemar by skin biopsy. Rhizopus oryzae identified on skin biopsy and A. fumigatus isolated on day 27 of 28 of culture from lung biopsy were not detected by cfDNA NGS, possibly due to lack of bloodstream penetration and questionable pathogenicity, respectively. Numerous DNA viruses were detected in patients with prolonged febrile neutropenia or abnormal imaging. Extended antifungal therapy was used in 73% of patients. Follow-up cfDNA sequencing in patients who were positive at enrollment was negative at 1 and 2 months. cfDNA NGS detected fungal pathogens from blood confirming its potential to guide treatment decisions in pediatric patients at risk for IFD and limit excessive empiric antifungal use. Future studies are needed to better understand the sensitivity and specificity of this approach.
Sections du résumé
BACKGROUND
We sought to determine if next-generation sequencing (NGS) of microbial cell-free DNA (cfDNA) in plasma would detect pathogens in pediatric patients at risk for invasive fungal disease (IFD).
PROCEDURES
Pediatric hematology, oncology, and stem cell transplant patients deemed at risk for new IFD had blood samples drawn at three time-points separated by 1-month intervals. The primary outcome measure was detection of fungal pathogens compared to standard clinical testing. Secondary outcomes included identification of other infectious pathogens, relationship to European Organization for Research and Treatment of Cancer's Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases' Mycoses Study Group (EORTC/MSG) guidelines, and assessment of antifungal therapy.
RESULTS
NGS identified fungal pathogens in seven of 40 at-risk patients for IFD and results were identical in four of six proven cases, including Aspergillus fumigatus by lung biopsy, Candida albicans by blood or pancreatic pseudocyst cultures, and Rhizopus delemar by skin biopsy. Rhizopus oryzae identified on skin biopsy and A. fumigatus isolated on day 27 of 28 of culture from lung biopsy were not detected by cfDNA NGS, possibly due to lack of bloodstream penetration and questionable pathogenicity, respectively. Numerous DNA viruses were detected in patients with prolonged febrile neutropenia or abnormal imaging. Extended antifungal therapy was used in 73% of patients. Follow-up cfDNA sequencing in patients who were positive at enrollment was negative at 1 and 2 months.
CONCLUSIONS
cfDNA NGS detected fungal pathogens from blood confirming its potential to guide treatment decisions in pediatric patients at risk for IFD and limit excessive empiric antifungal use. Future studies are needed to better understand the sensitivity and specificity of this approach.
Substances chimiques
Cell-Free Nucleic Acids
0
DNA, Fungal
0
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e27734Informations de copyright
© 2019 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.