New DNA Test Predicts Leukemia Infections
Researchers at St. Jude Children's Research Hospital have found that microbial cell-free DNA sequencing can predict bloodstream infections in children with leukemia. The breakthrough test can offer an early warning days before an infection becomes clinically apparent, potentially improving outcomes for vulnerable patients.
## New DNA Test Offers Early Warning for Leukemia Infections The groundbreaking test, known as microbial cell-free DNA (mcfDNA) sequencing, can identify circulating fragments of DNA from bacteria and fungi in a patient's blood. This allows for the detection of infections before the onset of symptoms like fever. The research, led by Dr. Joshua Wolf of St. Jude's Department of Host-Microbe Interactions, was recently published in *The Lancet Microbe*. For children with leukemia, whose immune systems are weakened by chemotherapy, bloodstream infections are a life-threatening complication that can lead to sepsis and death. These infections are a major reason why, even with high cure rates for the cancer itself, not all children survive. The current standard for detecting these infections is a blood culture, a method that has been in use for decades. The new DNA sequencing test demonstrated the ability to predict bloodstream infections in just over half of the cases up to three days before they would be diagnosed using current standards of care. A 2019 pilot study of the test on pediatric cancer patients showed a predictive sensitivity of 75% for all bloodstream infections and 80% for bacterial infections in the three days leading up to the onset of symptoms. The test also accurately ruled out infection in nearly 94% of samples from uninfected patients. A key advantage of the new test is its speed. The Karius test, a commercial version of this technology used in the St. Jude study, can deliver results the day after a blood sample is received at their lab. This is a significant improvement over traditional blood cultures, which can take 24 to 48 hours to yield a positive result. This time difference can be critical in starting targeted antibiotic treatment sooner. Bloodstream infections are a significant cause of death in children with acute lymphoblastic leukemia (ALL). Studies have shown that infections are the second leading cause of death after the cancer itself, accounting for about 35% of fatalities in some cohorts. One study found a 5-year cumulative incidence of infection-related death to be 2.4%. The current clinical trial for this predictive sequencing technology, known as PREDSEQ, is registered under NCT03226158 and has been actively recruiting patients. Researchers are now looking toward future clinical trials to determine how to best use this predictive information to guide preemptive treatment strategies. The challenge moving forward is to effectively act on the early warning provided by the test to improve patient outcomes.
