竺晓凡/阮敏团队发现外周血ctDNA是儿童AML患者MRD水平监测的重要标志
学术经纬约 5 分钟近期多项研究表明，循环肿瘤DNA（ctDNA）可以作为多种实体肿瘤和血液系统恶性肿瘤的疗效监测指标，但其对儿童AML患者MRD的动态监测作用有待进一步探索。该研究纳入了50例初诊AML患儿，所有患儿在初诊以及后续3个周期的化疗开始前（C2D1，C3D1及C4D1）共4个时间点，同时进行了骨髓流式细胞学（MFC），骨髓肿瘤基因二代测序（NGS）以及外周血ctDNA的检测。
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排版 | Sheila 校对 | uu
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靶向分析ctDNA有助于监测神母细胞瘤患者早期复发及发现可操作靶点
*本文由深圳市拾玉儿童公益基金会“儿童肿瘤前沿”团队编译或约稿，文中图表均源引自文献原文。本文著作权归文章作者所有，欢迎个人转发分享，未经允许禁止转载，作者拥有所有法定权利，违者必究。如需转载，请留言或联系[email protected]。本文旨在分享儿童肿瘤科研前沿成果，不是治疗方案推荐。如需获得疾病治疗方案指导，请前往正规医院就诊。
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原文摘要（Abstract）
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 myeloid 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 (NGS)-based BM-DNA and ctDNA was evaluated. Additionally, 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). Additionally, patients with >3 log reduction but without clearance in ctDNA were associated with an improved PFS as 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 AML patients, 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 necessitate an aggressive treatment plan due to improved survival, but this needs further study to delineate.
DOI: 10.1158/1078-0432.CCR-23-2589