A team at St. Jude Children’s Research Hospital has identified a potential way to predict bloodstream infections in children with high-risk leukemia several days earlier than possible with current standards of care. Using plasma microbial cell-free DNA sequencing (mcfDNA-Seq), the researchers were able to detect infection-causing pathogens in the blood before standard cultures. The findings, published in The Lancet Microbe, suggest that this tool could help clinicians start treatment sooner and protect immunocompromised children from severe illness.
Children undergoing chemotherapy for leukemia face a high risk of infection because their weakened immune systems cannot fight off ordinary bacteria and fungi. These infections often progress quickly to sepsis, delay chemotherapy, and can lead to death. Despite preventive measures, clinicians have lacked reliable ways to detect infections before symptoms develop. “We’re not good at predicting or preventing infections in children with cancer, and the consequences can be deadly,” said first author Joshua Wolf. “What we really need is a way to detect infections before they start, so we can treat kids earlier and save lives.”
In this prospective study, the team collected daily plasma samples from 158 pediatric patients with high-risk leukemia. Samples taken up to seven days before infection diagnosis were analyzed using mcfDNA-Seq, which identifies microbial DNA fragments circulating in the bloodstream. The test successfully predicted bloodstream infections in more than half of the cases up to three days before any symptoms appeared and ruled out infection in nearly 94% of uninfected patients. It also accurately detected the most common bacterial and fungal organisms associated with these infections.
“The infections we detect are the same ones that can cause sepsis and death,” said Wolf. “These findings provide a potential way to improve survival and outcomes for children with cancer or undergoing bone marrow transplantation.”
Importantly, this study evaluated mcfDNA-Seq not as a diagnostic test but as a predictive method to guide preemptive care. “The data can indicate when a patient is likely to get sick,” Wolf said. “The challenge now is figuring out how to act on that information effectively.”
Publication details: Wolf, Joshua et al. Predicting bloodstream infection by plasma cell-free metagenomic sequencing: a prospective cohort study. The Lancet Microbe. March 1, 2026.
Children undergoing chemotherapy for leukemia face a high risk of infection because their weakened immune systems cannot fight off ordinary bacteria and fungi. These infections often progress quickly to sepsis, delay chemotherapy, and can lead to death. Despite preventive measures, clinicians have lacked reliable ways to detect infections before symptoms develop. “We’re not good at predicting or preventing infections in children with cancer, and the consequences can be deadly,” said first author Joshua Wolf. “What we really need is a way to detect infections before they start, so we can treat kids earlier and save lives.”
In this prospective study, the team collected daily plasma samples from 158 pediatric patients with high-risk leukemia. Samples taken up to seven days before infection diagnosis were analyzed using mcfDNA-Seq, which identifies microbial DNA fragments circulating in the bloodstream. The test successfully predicted bloodstream infections in more than half of the cases up to three days before any symptoms appeared and ruled out infection in nearly 94% of uninfected patients. It also accurately detected the most common bacterial and fungal organisms associated with these infections.
“The infections we detect are the same ones that can cause sepsis and death,” said Wolf. “These findings provide a potential way to improve survival and outcomes for children with cancer or undergoing bone marrow transplantation.”
Importantly, this study evaluated mcfDNA-Seq not as a diagnostic test but as a predictive method to guide preemptive care. “The data can indicate when a patient is likely to get sick,” Wolf said. “The challenge now is figuring out how to act on that information effectively.”
Publication details: Wolf, Joshua et al. Predicting bloodstream infection by plasma cell-free metagenomic sequencing: a prospective cohort study. The Lancet Microbe. March 1, 2026.