Published today in The Lancet Microbe, a study led by corresponding author Joshua Wolf, PhD, MBBS, St. Jude Department of Host-Microbe Interactions, found that microbial cell-free DNA sequencing can detect bloodstream infections in children with leukemia days before symptoms appear, offering a potential path to earlier treatment and improved outcomes.
Researchers have identified a promising way to predict bloodstream infections in children with high-risk leukemia days before the infection would be diagnosed using current standards of care. The test, named plasma microbial cell-free DNA sequencing (mcfDNA-Seq), detected infection-causing pathogens days before standard blood cultures, offering a potential approach to protecting vulnerable patients by allowing treatment to start before the patient gets sick. The study was published today in The Lancet Microbe.
Bloodstream infections are a major threat to children undergoing treatment for leukemia. Chemotherapy weakens the immune system, making even common bacteria or fungi potentially life-threatening. These infections can quickly lead to sepsis, prolonged hospital stays, delayed chemotherapy and, in some cases, early mortality. Catching these infections early is critical, yet clinicians currently have no reliable method to identify infections before symptoms appear.
“We’re not good at predicting or preventing infections in children with cancer, and the consequences can be deadly, causing lasting damage or delaying chemotherapy, which reduces the chances of successful treatment,” said first and corresponding author Joshua Wolf, PhD, MBBS, St. Jude Department of Infectious Diseases. “Many infections still happen even with the best prevention strategies we have, so what we really need is a way to detect infections before they start, so we can treat kids earlier and save lives.”
Catching infections before symptoms
In this prospective study, researchers analyzed plasma samples collected daily from 158 pediatric patients with high-risk leukemia. They selected samples from up to seven days before and at diagnosis of a bloodstream infection and tested them using mcfDNA-Seq, a technology that detects fragments of microbial DNA circulating in the blood. mcfDNA-seq predicted bloodstream infections in just over half of cases up to three days before symptoms appeared. Additional analyses showed that the test reliably identified the most common bacteria and fungi that cause bloodstream infections in children with cancer, while accurately ruling out infection in 93.8% of samples from healthy or uninfected patients.
The findings suggest that mcfDNA-seq could one day become part of a proactive approach to infection management in children receiving intensive cancer therapy. “The infections we detect are the same ones that can cause sepsis and death,” Wolf said. “These findings provide a potential way to improve survival and outcomes for children with cancer or undergoing bone marrow transplantation.”
This research also represents a novel use of mcfDNA-seq, not as a diagnostic tool after infection appears, but as a predictive method to guide preemptive treatment. Unlike previous studies focused on proving the technology itself works, the St. Jude team independently evaluated how well it predicted infections in a real-world patient population.
“The data can indicate when a patient is likely to get sick,” Wolf continued. “The challenge now is figuring out how to act on that information effectively.”
While further clinical trials are needed to evaluate how best to incorporate this approach in treatment decisions, the study demonstrates the promise of this technology to change the way infections are anticipated and managed in high-risk patients. Early detection with mcfDNA-Seq could allow clinicians to intervene sooner, potentially preventing serious complications, reducing hospitalizations and improving outcomes for immunocompromised children.
Authors and funding
The study’s other authors are Kathryn Goggin, Kim Allison, Gabriela Maron, Jose Ferrolino, Lauren Lazure, Christina Kohler, Abigail Brenner, Yilun Sun, Li Tang, Veronica Gonzalez-Pena, Jeffrey Rubnitz, Charles Gawad and Elisa Margolis, all of St. Jude; Paul Thomas, formerly of St. Jude, Yuki Inaba, University of Tennessee Health Science Center; and Asim Ahmed, MD, Boston Children’s Hospital.
The study was supported by grants from the National Cancer Institute (CA21765 and R25CA23944), the St. Jude Children’s Research Hospital Comprehensive Cancer Center Developmental Funds Award and ALSAC, the fundraising and awareness organization of St. Jude.
St. Jude Children's Research Hospital
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