Measurable residual disease (MRD) is a strong predictor of relapse in acute myeloid leukemia (AML) patients who have undergone bone marrow transplantation. But the detection of residual leukemic cells requires repeated bone marrow biopsies, which are invasive and painful. Researchers led by Ludwig Johns Hopkins’ Yuxuan Wang, Bert Vogelstein and Nickolas Papadopoulos, with their Johns Hopkins colleagues Lukasz Gondek and Richard Jones, reported in a PNAS publication in April a personalized, plasma-based assay for detecting MRD called v96. The assay incorporates up to 96 mutations and can be used to detect MRD with far greater ease and accuracy than that achieved by existing assays. The researchers tested v96 on 30 patients and found that it detected MRD in all patients in remission prior to transplantation—where conventional clinical assays found it in only 20% of them. Moreover, in 27 of the 30 patients (90% of patients), evidence of residual disease was found two months after transplantation. Cell-free DNA from plasma detected leukemic cells with far greater sensitivity than DNA isolated from bone marrow cells. In patients who relapsed, the median number of mutants detected in plasma was 352 times higher than in those who remained in remission. The researchers noted that noninvasive assays could reliably guide “the timing of transplantation and subsequent therapeutic measures” for AML, and should be evaluated in larger prospective studies.
A plasma-based DNA test for quantification of disease burden in acute myeloid leukemia patients undergoing bone marrow transplantation
PNAS, 2026 April 14