Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios

• DOI: 10.3389/fmolb.2023.1333943
• Publication Date: 2024-01-22T14:09:36Z
• Authors: Noreen Grace George; Bhavika Rishi; Amitabh Singh; Sree Vishmaya; Rakesh Kumar; Neetu Kushwaha; Manpreet Kaur; Reena Bhardwaj; Ankur Jain; Aditi Jain; Sumita Chaudhry; Aroonima Misra
• Keywords: 0301 basic medicine; bone marrow; complete remission; QH301-705.5; acute lymphoblastic leukemia; Biochemistry, Genetics and Molecular Biology (miscellaneous); Biochemistry; ratio of cell-free DNA at diagnosis/remission acute myeloid leukemia; 03 medical and health sciences; Molecular Biosciences; prognosis; Biology (General); Molecular Biology

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis.Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cfDNA extraction kits. The probability of poor outcomes in high-risk groups and a cut-off value for risk stratification minimal residual disease (MRD) positivity and outcome prediction were derived.Results: Twenty-five patients diagnosed with AML and ALL were risk-stratified based on NCI risk stratification, and of these 25 patients, 4 patients were of standard risk (SR) and 1 patient was of intermediate risk (IR), while a majority of patients (80%) were of high risk (HR). Of these, four HR patients passed away. The ratio of cfDNA reduction at baseline and the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of the MRD status. A cfDNA ratio score of 2.6 or higher at diagnosis/remission predicted poor outcomes, with higher accuracy than conventional MRD detection by flow cytometry.Conclusion: A higher cfDNA ratio at diagnosis/remission or at baseline predicts poor outcomes in acute leukemia patients. This pilot study suggests that cfDNA ratio scoring may be a useful tool for predicting prognosis in acute leukemia patients, regardless of the MRD status.