Acute myeloid leukemia (AML) is among the most aggressive forms of blood cancer, and while modern medicine can often push it into remission, the threat of a relapse remains a constant fear for patients.

Now, a step forward in genetic testing could help doctors look deeper than ever before to predict a patient's future health.

In a series of studies published recently in Bone Marrow Transplantation, researchers revealed that a specialized DNA-based test can identify tiny traces of cancer that traditional methods often miss. 

This hidden cancer is called measurable residual disease (MRD). By finding these microscopic markers, doctors can better understand which patients are at the highest risk after a stem cell transplant.

The latest research focused on a specific gene called NPM1. 

This mutation appears in roughly 30% of adults diagnosed with AML. Many of these patients undergo a stem cell transplant to replace diseased marrow with healthy donor cells, but success of the procedure often hinges on how much cancer was left behind before the transplant started.

Using next-generation DNA sequencing, the team analyzed blood samples from 190 patients. The test was so sensitive it could find the mutation in fewer than 1 in 10,000 cells.

The blood samples had been stored in a national biobank for U.S. patients who received allogeneic hematopoietic cell transplantation (alloHCT) between 2013 and 2019.

The results were stark: Patients who tested positive for the mutated NPM1 signal before their transplant were three to four times more likely to see their cancer return. Furthermore, those with the highest levels of the NPM1 marker had a 27% chance of surviving three years after their procedure.

Researchers also noted that the NPM1 mutation often occurs alongside the FLT3-ITD mutation, and when a single test is available, they found that testing for NPM1 provided the most predictive value overall.

This research is part of a larger effort to move away from one-size-fits-all cancer care and toward precision medicine. By tailoring tests to the specific mutations found in an individual's blood, doctors can monitor recovery with much higher accuracy.

“Large, carefully designed studies are essential for systematically improving the standards in how we monitor and treat this rare disease,” said senior author Christopher Hourigan, a professor and director of the Cancer Research Center at the Fralin Biomedical Research Institute in Roanoke, Virginia. 

“Some genetic markers may appear promising, but without strong evidence they can be misleading," he added in a news release. "Precision medicine depends on building a solid foundation so these powerful technologies can be used responsibly."

The team is now expanding and validating its work through a nationwide study called MEASURE, which is active at 18 major cancer centers across the United States. 

“Precision medicine depends on building a solid foundation so these powerful technologies can be used responsibly,” Hourigan added.

The results of that work are expected to be available at year’s end.

Hourigan leads the Foundation for the National Institutes of Health Acute Myeloid Leukemia Measurable Residual Disease Biomarkers Consortium.

It includes researchers from Virginia Tech, Dana-Farber Cancer Institute of Harvard Medical School and Fred Hutch Cancer Center, along with representatives from the U.S. Food and Drug Administration and more than 20 pharmaceutical and medical diagnostic companies. 

The work was also supported by Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health and the Red Gates Foundation.