{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T18:39:48Z","timestamp":1785091188277,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Karius, Inc., provided testing and supplies"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We sought to determine if next\u2010generation sequencing (NGS) of microbial cell\u2010free DNA (cfDNA) in plasma would detect pathogens in pediatric patients at risk for invasive fungal disease (IFD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>Pediatric hematology, oncology, and stem cell transplant patients deemed at risk for new IFD had blood samples drawn at three time\u2010points separated by 1\u2010month 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\u2019 Mycoses Study Group (EORTC\/MSG) guidelines, and assessment of antifungal therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NGS identified fungal pathogens in seven of 40 at\u2010risk patients for IFD and results were identical in four of six proven cases, including <jats:italic>Aspergillus fumigatus<\/jats:italic> by lung biopsy, <jats:italic>Candida albicans<\/jats:italic> by blood or pancreatic pseudocyst cultures, and <jats:italic>Rhizopus delemar<\/jats:italic> by skin biopsy. <jats:italic>Rhizopus oryzae<\/jats:italic> identified on skin biopsy and <jats:italic>A. fumigatus<\/jats:italic> 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\u2010up cfDNA sequencing in patients who were positive at enrollment was negative at 1 and 2 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.27734","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T03:45:37Z","timestamp":1554263137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Cell\u2010free DNA next\u2010generation sequencing successfully detects infectious pathogens in pediatric oncology and hematopoietic stem cell transplant patients at risk for invasive fungal disease"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7784-0476","authenticated-orcid":false,"given":"Amy E.","family":"Armstrong","sequence":"first","affiliation":[{"name":"Division of Hematology Oncology and Transplantation Ann &amp; Robert H. Lurie Children's Hospital of Chicago  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0471-9883","authenticated-orcid":false,"given":"Jenna","family":"Rossoff","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology and Transplantation Ann &amp; Robert H. Lurie Children's Hospital of Chicago  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4971-9334","authenticated-orcid":false,"given":"Desiree","family":"Hollemon","sequence":"additional","affiliation":[{"name":"Karius, Inc.  Redwood City California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Hong","sequence":"additional","affiliation":[{"name":"Karius, Inc.  Redwood City California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Ann &amp; Robert H. Lurie Children's Hospital of Chicago  Chicago Illinois"},{"name":"Department of Pediatrics Northwestern University Feinberg School of Medicine  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Chaudhury","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology and Transplantation Ann &amp; Robert H. 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