Blood Test Identifies AML Patients at Risk of Posttransplant Relapse
A small portion of acute myeloid leukemia patients in remission showed persisting mutations, which predicted their risk of death from cancer relapse
Researchers at the National Institutes of Health show 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 to develop precision medicine and personalized posttransplant care for these patients.
About 20,000 adults in the US are diagnosed each year 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.
Current study and striking findings
Researchers in the current study wanted to show that screening patients in remission for evidence of low levels of leukemia using standardized genetic testing could better predict their 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, WI.
After screening adults with variants commonly associated with AML, researchers showed that the two most common mutations in AML—NPM1 and FLT3-ITD—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 still 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 percent of patients with the lingering NPM1 and FLT3-ITD mutations relapsed and just 39 percent survived after three years. In comparison, only 21 percent of adults without this evidence of trace leukemia relapsed after three years, and 63 percent 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 percent chance of relapse or if I am the one with a 70 percent chance of relapse,” said Christopher S. Hourigan, MD, PhD, study lead senior investigator and chief of the Laboratory of Myeloid Malignancies, part of the National Heart, Lung, and Blood Institute’s (NHLBI) Intramural Program.
“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,” said Hourigan. “For that one person out of six, the transplant often isn’t going to be enough. Other options might also include enrolling in a clinical research trial or considering additional or different therapies.”
Critical data for pretransplant decisions
“This study confirms prior research and provides new important data showing why testing for residual disease before a transplant is critical,” said Rear Admiral Richard Childs, MD, clinical director and acting scientific director of NHLBI. “This information can also empower physicians to tailor transplant strategies, including considering different pretransplant conditioning regimens and chemotherapies, to reduce an AML patient’s risk for relapse and improve their long-term chance for survival.”
In their analysis, the researchers also observed that adults with persistent mutations, but who were younger than 60 years of age and received higher doses of chemotherapy and/or radiotherapy as part of their transplant preparation, were more likely to remain cancer-free after three years than those receiving lower doses.
They also found that adults who didn’t receive stronger treatment before the transplant, which is now recommended as part of clinical guidelines, did better when this lower-dose therapy included a chemotherapy drug melphalan. However, more research is needed to evaluate these potential benefits and other treatments, including targeted therapy for the FLT3-ITD mutation.
“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 James H. Doroshow, MD, deputy director for Clinical and Translational Research at the National Cancer Institute (NCI).
AML accounts for 1 percent of all new cancer cases, and adults ages 65 and older are more likely to receive a diagnosis.
This study was funded by NHLBI, NCI, the National Institute of Allergy and Infectious Diseases, the Health Resources and Services Administration, the Office of Naval Research, and the NIH Director’s Challenge Innovation Award. The Laboratory of Myeloid Malignancies received additional funding from Sellas and the Foundation of the NIH AML MRD Biomarkers Consortium.
- This press release was originally published on the National Institutes of Health website