医学
微小残留病
一致性
髓系白血病
肿瘤科
内科学
循环肿瘤DNA
数字聚合酶链反应
白血病
前瞻性队列研究
癌症
聚合酶链反应
生物
基因
遗传学
作者
Li-Peng Liu,Su-Yu Zong,Ao‐Li Zhang,Yuan-Yuan Ren,Ben-Quan Qi,Lixian Chang,Wenyu Yang,Xiaojuan Chen,Yu-Mei Chen,Li Zhang,Yao Zou,Ye Guo,Yingchi Zhang,Min Ruan,Xiaofan Zhu
标识
DOI:10.1158/1078-0432.ccr-23-2589
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 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.
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