Researchers on the National Institutes of Health show the advantages 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 geared toward developing precision medicine and personalized post-transplant take care of these patients.

About 20,000 adults in the US are diagnosed every 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 possibilities. Nonetheless, research has shown that lingering traces of leukemia could make a transplant less effective.

Researchers in the present study wanted to point out that screening patients in remission for evidence of low levels of leukemia using standardized genetic testing could higher predict their three-year risks for relapse and survival. To do this, 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 related to AML, researchers showed that the 2 most typical mutations in AML – NPM1 and FLT3-ITD – could possibly be used to trace residual leukemia. Amongst 822 adults with these variants detectable at initial diagnosis, 142 adults – about 1 in 6 – were found to still have residual traces of those 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 NPM1 and FLT3-ITD mutations relapsed and just 39% survived after three years. As compared only 21% of adults without this evidence of trace leukemia relapsed after three years and 63% survived.  

If I’m one in every of six people waiting in a health care provider’s office and we’re all being told we’re entering into for a transplant and we have the identical risk, I would like to know if I’m actually one in every of those five who has a 20% probability of relapse or if I’m the one with a 70% probability of relapse.”

Christopher S. Hourigan, M.D., D.Phil., study lead, senior investigator and chief of the Laboratory of Myeloid Malignancies, a part of the National Heart, Lung, and Blood Institute’s (NHLBI) Intramural Program

“Having this increased risk for relapse may not impact an individual’s decision about having a bone marrow transplant, however it could influence their next steps in care,” Hourigan said. “For that one person out of six, the transplant often is not 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 recent necessary data showing why testing for residual disease before a transplant is critical,” said Rear Admiral Richard Childs, M.D., clinical director and acting scientific director of NHLBI. “This information may also empower physicians to tailor transplant strategies, including considering different pre-transplant conditioning regimens and chemotherapies, to cut back an AML patient’s risk for relapse and improve their long-term probability for survival.”

Of their evaluation, the researchers also observed that adults with persistent mutations, but who were younger than age 60 and received higher doses of chemotherapy and/or radiotherapy as a part of their transplant preparation, were more more likely to remain cancer free after three years than those receiving lower doses.

Additionally they found that adults who didn’t receive stronger treatment before the transplant, which is now beneficial as a part of clinical guidelines, did higher when this lower-dose therapy included a chemotherapy drug melphalan. Nonetheless, more research is required to judge these potential advantages and of other treatments, including targeted therapy for the FLT3-ITD mutation.  

“Finding daring and revolutionary approaches, including precision therapy for AML, is important to the Biden Administration’s goal to chop the death rate from cancer in half inside the subsequent 25 years,” said James H. Doroshow, M.D., Deputy Director for Clinical and Translational Research on the National Cancer Institute (NCI).

AML accounts for 1% of all recent cancer cases, and adults ages 65 and older usually tend 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 has received additional funding from Sellas and the Foundation of the NIH AML MRD Biomarkers Consortium.

Source:

National Institutes of Health

Journal reference:

Dillon, L.W., et al. (2023) DNA sequencing to detect residual disease in adults with acute myeloid leukemia prior to hematopoietic cell transplant. JAMA. doi.org/10.1001/jama.2023.1363.