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Cell-free DNA Sequencing Enhances Antimicrobial Management

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The Impact of Next-Generation Sequencing Cell-free Pathogen DNA Test on Antimicrobial Management in Adults with Hematological Malignancies and Transplant Recipients with Suspected Infections


Collaborative Research Study Published in Transplantation and Cellular Therapy


James Yu1, Juan D. Diaz2, Steven C. Goldstein3, Rushang D. Patel3, Juan C. Varela3, Caralyn Reyenga3, Megan Smith3, Tori Smith3, Jason Balls3, Sarfraz Ahmad4, Shahram Mori3


1 Department of Internal Medicine, 2Section of Infectious Disease, 3Blood & Marrow Transplant

Center, 4Gynecologic Oncology Program, AdventHealth Cancer Institute, Orlando, FL 32804


comparison images of a cell



Background: Infections in adult patients with hematological malignancies (HM) and stem cell transplant (SCT) recipients are a significant cause of morbidity and mortality. A timely diagnosis of infections can have a major impact on outcomes. Tools that help rule out infectious causes of fever can decrease antibiotic use, toxicities, hospitalization costs and potentially decrease antibiotic resistance in the long term.


Objective: We retrospectively evaluated the ability of cell-free DNA next-generation sequencing (NGS) test in the timely identification of pathogenic microorganisms, and its impact on the antimicrobial management of immunocompromised patients with hematologic malignancies.


Study Design: In the period between 2018-2020, ninety-five samples were reviewed, of which 31 adult patients (32 tests) had hematologic malignancies or were recipients of SCT. The NGS tests were performed in the following patients: a) patients with prolonged fever and negative conventional tests, b) persistent fever despite positive conventional test and appropriate antimicrobials, and c) afebrile patients with imaging suspicious for infection.


Results: The median time from fever to NGS sampling was five-days (range: 1-28). The median time to NGS results was two-days (range: 1-6). The NGS resulted in an escalation of antibiotics in 28% of cases (9/32) and de-escalation of antibiotics in 31% of cases (10/32). Overall, NGS testing changed management in nearly 59% (19/32) of patients. The sensitivity and specificity of NGS to detect clinically significant infection was 80% and 58%, respectively. The test identified uncommon and difficult to diagnose organisms such as Nocardia, Legionella, Toxoplasma and Pneumocystis jirovecii, resulting in rapid antimicrobial interventions.


Conclusion: In patients with HM or SCT recipients, microbial cell-free DNA sequencing allowed rapid and actionable treatment. This strategy can target appropriate antibiotic use, avoid over-treatment and potentially decrease the hospital length-of-stay.



  • Cell-free DNA (cfDNA) has reasonably high sensitivity and specificity.
  • cfDNA rapidly identified opportunistic/fungal infection in immunocomprised patients.
  • Identification can result in early intervention and better anti-microbial stewardship.
  • cfDNA may help decrease unnecessary broad spectrum anti-microbial use.


For more information or to refer a patient, call Bone Marrow Transplant Nurse Navigators Austin Carroll, BSN, RN; Anna Cullivan, BSN, RN; Vielka Hernandez, RN; or Amber Sipes, RN, at Call407-303-2825.

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