Blood Test Identifies AML Patients at Greater Risk for Relapse After Transplant
Researchers at NIH showed the benefits of screening adult patients in remission from acute myeloid leukemia (AML) for residual disease before receiving a bone marrow transplant.
The findings, published in JAMA, support ongoing research aimed at developing precision medicine and personalized post-transplant care for these patients.
About 20,000 adults in the U.S. are diagnosed annually with AML, a deadly blood cancer, and about one in three live past five years. A bone marrow transplant, which replaces unhealthy blood-forming cells with healthy cells from a donor, often improves these chances. However, research has shown that lingering traces of leukemia can make a transplant less effective.
In the current study, researchers wanted to show that screening patients in remission for evidence of low levels of leukemia using standardized genetic testing could better predict three-year risks for relapse and survival.
To do that, they used ultra-deep DNA sequencing technology to screen blood samples from 1,075 adults in remission from AML. All were preparing to have a bone marrow transplant. The study samples were provided through donations to the Center for International Blood and Marrow Transplant Research.
After screening adults with variants commonly associated with AML, researchers showed that the two most common mutations in AML could be used to track residual leukemia. Among 822 adults with these variants detectable at initial diagnosis, 142 adults—about one in six—were found to have residual traces of these mutations after therapy despite being classified as in remission.
The researchers found the outcomes for these patients striking. Nearly 70% of patients with the lingering mutations relapsed and just 39% survived after three years. In comparison, only 21% of adults without this evidence of trace leukemia relapsed after three years and 63% survived.
“If I’m one of six people waiting in a doctor’s office and we’re all being told we’re going in for a transplant and we’ve got the same risk, I want to know if I’m actually one of those five who has a 20% chance of relapse or if I am the one with a 70% chance of relapse,” said study lead Dr. Christopher Hourigan, senior investigator and chief of NHLBI’s Laboratory of Myeloid Malignancies.
“Having this increased risk for relapse may not impact a person’s decision about having a bone marrow transplant, but it could influence their next steps in care,” Hourigan said. “For that one person out of six, the transplant often isn’t going to be enough. Other options might include also enrolling in a clinical research trial or considering additional or different therapies.”
“This study confirms prior research and provides new important data showing why testing for residual disease before a transplant is critical,” said Rear Admiral Dr. Richard Childs, NHLBI clinical director and acting scientific director. “This information can also empower physicians to tailor transplant strategies…to reduce an AML patient’s risk for relapse and improve their long-term chance for survival.”
“Finding bold and innovative approaches, including precision therapy for AML, is essential to the Biden Administration’s goal to cut the death rate from cancer in half within the next 25 years,” said Dr. James Doroshow, NCI deputy director for clinical and translational research.
The study was funded by NHLBI, NCI, NIAID, the Health Resources and Services Administration, the Office of Naval Research and the NIH Director’s Challenge Innovation Award.