DNA Sequencing May Help Identify AML Patients at Greater Risk for Relapse After BMT

March 09, 2023

Screening adult patients in remission from acute myeloid leukemia (AML) for residual disease prior to bone marrow transplant (BMT) may help identify patients at higher risk for relapse, according to findings published this week in JAMA. BMT often improves a patient’s chance of survival, but research has shown that lingering traces of leukemia may make a transplant less effective.

In this study, investigators used ultra-deep DNA sequencing technology to screen blood samples from 1,075 adults in remission from AML who were preparing for BMT (divided into discovery and validation cohorts based on BMT date). After screening for 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.

In total, 822 patients had NPM1 and/or FLT3-ITD variants present at their initial AML diagnosis. Investigators found that 142 adults still had residual traces of these mutations after therapy (an allele fraction of 0.01% or higher), despite being classified as in remission. Three years post-BMT, nearly 70% of patients with the lingering NPM1 and FLT3-ITD mutations relapsed while 39% survived. In comparison, 21% of adults without evidence of trace leukemia relapsed after three years while 63% survived. Furthermore, results demonstrated that, among patients with persistent mutations, those who received higher doses of chemotherapy and/or radiotherapy as part of their transplant preparation were more likely than those who received lower doses to remain cancer-free after three years.

According to investigators, the findings indicate that adults with persistence of FLT3-ITD and/or NPM1 variants while in remission after their initial treatment for AML represent patients with unmet medical need. As such, they should be offered enrollment in a therapeutic clinical trial wherever possible.

“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,” Christopher S. Hourigan, MD, DPhil, senior investigator and chief of the Laboratory of Myeloid Malignancies in the National Heart, Lung, and Blood Institute’s Intramural Program, said in a media release. “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.” 

Investigators concluded that further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with AML.