M1. Clinical studies of fungal infections
Oral Abstract Submission
Joshua A. Hill, MD
Fred Hutchinson Cancer Research Center; University of Washington
Disclosure: Amplyx: Consultant
Karius: Grant/Research Support
Nohla therapeutics: Consultant
Shire: Grant/Research Support
Michael Boeckh, MD PhD
Fred Hutchinson Cancer Research Center
Disclosure: Ablynx: Consultant, Grant/Research Support
Ansun Biopharma: Consultant, Grant/Research Support
Astellas: Consultant, Grant/Research Support
Bavarian Nordic: Consultant
Chimerix: Consultant, Grant/Research Support
Gilead: Consultant, Grant/Research Support
Janssen: Consultant, Grant/Research Support
Lophius: Grant/Research Support
Merck: Consultant, Grant/Research Support
Shire: Consultant, Grant/Research Support
Vir Bio: Consultant, Grant/Research Support
Pulmonary invasive mold infections (IMI) cause significant morbidity and mortality after hematopoietic cell transplant (HCT). Non-invasive diagnostic options are limited, particularly for non-Aspergillus (non-Asp) molds. Given differences in activity and toxicities of antifungals, early diagnosis and targeting of specific IMI is important. We evaluated the performance of the Karius Test, a plasma microbial cell-free DNA next-generation sequencing (NGS) test, for detecting IMI in HCT recipients.
We conducted a retrospective case-control study of 24 HCT recipients with proven non-Asp pulmonary IMI, 51 probable/proven Aspergillus pulmonary IMI, and 20 controls with non-fungal pulmonary infections. All subjects had plasma obtained within 14 days of diagnosis. Workup included bronchoalveolar lavage (BAL) and/or biopsy, with fungal stains/culture and galactomannan testing of BAL and serum. Plasma cell-free DNA was extracted and NGS performed (Karius, Redwood City, CA). Human reads were removed and remaining sequences aligned to a curated database including over 300 fungi. Organisms present above a predefined significance threshold were reported. A higher sensitivity research-use only pipeline was also used. Analysis of sequencing data was blinded to all clinical data.
The Karius plasma NGS test is a non-invasive means of detecting IMI with high sensitivity for non-Aspmolds in HCT recipients with pulmonary disease. Further assay optimization may increase sensitivity for Aspergillus. This may be a useful adjunctive test for diagnosing IMI, and larger studies should be conducted.