Early Detection of Molecular Residual Disease and Risk Stratification for Children with Acute Myeloid Leukemia via Circulating Tumor DNA
©2024 American Association for Cancer Research..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 30(2024), 6 vom: 15. März, Seite 1143-1151 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Li-Peng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-23-2589 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Early Detection of Molecular Residual Disease and Risk Stratification for Children with Acute Myeloid Leukemia via Circulating Tumor DNA |
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| 520 | |a ©2024 American Association for Cancer Research. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Circulating Tumor DNA |2 NLM | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 700 | 1 | |a Zong, Su-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ao-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Yuan-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Ben-Quan |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Li-Xian |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Wen-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiao-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yu-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Ye |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ying-Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Ruan, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xiao-Fan |e verfasserin |4 aut | |
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