Pre-Transplant DNA Sequencing Suggests Association Between Persistence of Most-Common AML Variants and Poorer Outcomes in Patients with AML

Rates of relapse and worse survival were associated with persistent FLT3-ITD or NPM1 variants prior to allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia.

Detection by DNA sequencing of persistent FLT3-ITD or NPM1 variants – the two most common AML variants – in blood ahead of allogeneic hematopoietic cell transplantation (allo-HCT) in adult patients with acute myeloid leukemia (AML) that was in remission was associated with significantly increased rates of relapse and worse survival compared with patients who did not have these variants.

DNA sequencing was retrospectively performed on pretransplant blood from 1,075 patients aged 18 or older who had received a first allo-HCT during a first remission of AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT. All transplants were performed between 2013 and 2019 at 111 treatment sites in the United States. The study, led by Christopher S. Hourigan, DM, DPhil, of the National Heart, Lung, and Blood Institute at the National Institutes of Health, was published in the Journal of the American Medical Association in March.

Persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or above with statistically significantly increased rates of relapse and decreased survival, the authors write. These results show that, in this group of patients, MRD testing by next-generation sequencing “could identify differential risk between individuals otherwise placed in the same baseline risk classification.”

“Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with [AML],” they conclude.

Reference

Dillon LW, Gui G, Page KM, et al. DNA sequencing to detect residual disease in adults with acute myeloid leukemia prior to hematopoietic cell transplant. JAMA. 2023;329(9):745-755. doi:10.1001/jama.2023.1363