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Updated: Jul 6, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Early Detection of Molecular Residual Disease and Risk Stratification for Children with Acute Myeloid Leukemia via
Li-Peng Liu1,2, Su-Yu Zong1,2, Ao-Li Zhang1,2
1Division of Pediatric Blood Diseases Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Purpose:
Patient-tailored minimal residual disease (MRD) monitoring based on circulating tumor DNA (ctDNA) sequencing of leukemia-specific mutations enables early detection of relapse for pre-emptive treatment, but its utilization in pediatric acute myelogenous leukemia (AML) is scarce. Thus, we aim to examine the role of ctDNA as a prognostic biomarker in monitoring response to the treatment of pediatric AML.
Experimental Design:
A prospective longitudinal study with 50 children with AML was launched, and sequential bone marrow (BM) and matched plasma samples were collected. The concordance of mutations by next-generation sequencing-based BM-DNA and ctDNA was evaluated. In addition, progression-free survival (PFS) and overall survival (OS) were estimated.
Results:
In 195 sample pairs from 50 patients, the concordance of leukemia-specific mutations between ctDNA and BM-DNA was 92.8%. Patients with undetectable ctDNA were linked to improved OS and PFS versus detectable ctDNA in the last sampling (both P < 0.001). Patients who cleared their ctDNA post three cycles of treatment had similar PFS compared with persistently negative ctDNA (P = 0.728). In addition, patients with >3 log reduction but without clearance in ctDNA were associated with an improved PFS as were patients with ctDNA clearance (P = 0.564).
Conclusions:
Thus, ctDNA-based MRD monitoring appears to be a promising option to complement the overall assessment of pediatric patients with AML, wherein patients with continuous ctDNA negativity have the option for treatment de-escalation in subsequent therapy. Importantly, patients with >3 log reduction but without clearance in ctDNA may not require an aggressive treatment plan due to improved survival, but this needs further study to delineate.
Insights
Circulating tumor DNA (ctDNA) monitoring shows promise for pediatric acute myelogenous leukemia (AML). Undetectable ctDNA correlates with better survival, suggesting its role in guiding treatment decisions.
Area of Science:
- Oncology
- Genetics
- Pediatrics
Background:
- Minimal residual disease (MRD) monitoring using circulating tumor DNA (ctDNA) aids early relapse detection in leukemia.
- Utilization of ctDNA for MRD monitoring in pediatric acute myelogenous leukemia (AML) is limited.
Purpose of the Study:
- To investigate the prognostic value of ctDNA in monitoring treatment response in pediatric AML.
- To evaluate ctDNA as a biomarker for predicting outcomes in pediatric AML patients.
Main Methods:
- Prospective longitudinal study involving 50 children with AML.
- Collection of sequential bone marrow (BM) and plasma samples for DNA analysis.
- Next-generation sequencing (NGS) to assess ctDNA and BM-DNA mutation concordance, and estimation of progression-free survival (PFS) and overall survival (OS).
Main Results:
- High concordance (92.8%) between ctDNA and BM-DNA mutations observed.
- Undetectable ctDNA significantly correlated with improved OS and PFS (P < 0.001).
- Patients achieving ctDNA clearance or >3 log reduction showed improved PFS, though not statistically significant in the latter case (P = 0.564).
Conclusions:
- ctDNA-based MRD monitoring is a valuable tool for assessing pediatric AML patients.
- Continuous ctDNA negativity may allow for treatment de-escalation.
- Further research is needed to confirm the survival benefits for patients with significant ctDNA reduction but without complete clearance.
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