Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer
AuthorGoggin, KP; Gonzalez-Pena, V; Inaba, Y; Allison, KJ; Hong, DK; Ahmed, AA; Hollemon, D; Natarajan, S; Mahmud, O; Kuenzinger, W; ...
Source TitleJAMA Oncology
PublisherAMER MEDICAL ASSOC
University of Melbourne Author/sWolf, Joshua
Document TypeJournal Article
CitationsGoggin, K. P., Gonzalez-Pena, V., Inaba, Y., Allison, K. J., Hong, D. K., Ahmed, A. A., Hollemon, D., Natarajan, S., Mahmud, O., Kuenzinger, W., Youssef, S., Brenner, A., Maron, G., Choi, J., Rubnitz, J. E., Sun, Y., Tang, L., Wolf, J. & Gawad, C. (2020). Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer. JAMA ONCOLOGY, 6 (4), pp.552-556. https://doi.org/10.1001/jamaoncol.2019.4120.
Access StatusOpen Access
Importance: Bloodstream infection (BSI) is a common, life-threatening complication of treatment for cancer. Predicting BSI before onset of clinical symptoms would enable preemptive therapy, but there is no reliable screening test. Objective: To estimate sensitivity and specificity of plasma microbial cell-free DNA sequencing (mcfDNA-seq) for predicting BSI in patients at high risk of life-threatening infection. Design, Setting, and Participants: A prospective pilot cohort study of mcfDNA-seq for predicting BSI in pediatric patients (<25 years of age) with relapsed or refractory cancers at St Jude Children's Research Hospital, a specialist quaternary pediatric hematology-oncology referral center. Remnant clinical blood samples were collected during chemotherapy and hematopoietic cell transplantation. Samples collected during the 7 days before and at onset of BSI episodes, along with negative control samples from study participants, underwent blinded testing using a mcfDNA-seq test in a Clinical Laboratory Improvement Amendments/College of American Pathologists-approved laboratory. Main Outcomes and Measures: The primary outcomes were sensitivity of mcfDNA-seq for detecting a BSI pathogen during the 3 days before BSI onset and specificity of mcfDNA-seq in the absence of fever or infection in the preceding or subsequent 7 days. Results: Between August 9, 2017, and June 4, 2018, 47 participants (27 [57%] male; median age [IQR], 10 [5-14] years) were enrolled; 19 BSI episodes occurred in 12 participants, and predictive samples were available for 16 episodes, including 15 bacterial BSI episodes. In the 3 days before the onset of infection, predictive sensitivity of mcfDNA-seq was 75% for all BSIs (12 of 16; 95% CI, 51%-90%) and 80% (12 of 15; 95% CI, 55%-93%) for bacterial BSIs. The specificity of mcfDNA-seq, evaluated on 33 negative control samples from enrolled participants, was 82% (27 of 33; 95% CI, 66%-91%) for any bacterial or fungal organism and 91% (30 of 33; 95% CI, 76%-97%) for any common BSI pathogen, and the concentration of pathogen DNA was lower in control than predictive samples. Conclusions and Relevance: A clinically relevant pathogen can be identified by mcfDNA-seq days before the onset of BSI in a majority of episodes, potentially enabling preemptive treatment. Clinical application appears feasible pending further study. Trial Registration: ClinicalTrials.gov identifier: NCT03226158.
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