在经过治疗的AML患者中，由于残存的低水平克隆，通常存在可测量的残留疾病（MRD）。这项研究评估了NGS检测到的治疗后残留体细胞突变是否对后续临床结果有重大预测意义。128名AML患者进行了同一42基因MRD-验证NGS检测的术前和术后检测。诱导后，59名（46％）患者突变阴性（0.0024 VAF检测限制），69名（54％）仍有≥1个NGS检测可见的残留突变。与NGS阴性患者相比，NGS阳性患者的总生存期更短（17个月对中位数未达到；P = 0.004；风险比为2.2 [95％ CI：1.3-3.7]），复发时间也更短（14个月对中位数不到；P = 0.014；HR = 1.9 [95％ CI：1.1-3.1]）。在95名完全形态学缓解（CR）的患者中，43名（45％）通过NGS检测为MRD阳性，52名（55％）为MRD阴性。这些MRD阳性的CR患者的总生存期较短（16.8个月对中位数未达到；P = 0.013；HR = 2.1 [95％ CI：1.2-3.9]）比MRD阴性的CR患者更短。因此，用诊断时相同的NGS检测定义的治疗后持续的MRD阳性是低水平白血病克隆的更敏感的生物标志物，比传统的非分子学方法更具预后价值。©2023年作者。

Treated AML patients often have measurable residual disease (MRD) due to persisting low-level clones. This study assessed whether residual post-treatment somatic mutations, detected by NGS, were significantly prognostic for subsequent clinical outcomes. AML patients (n = 128) underwent both pre-and post-treatment testing with the same 42-gene MRD-validated NGS assay. After induction, 59 (46%) patients were mutation-negative (0.0024 VAF detection limit) and 69 (54%) had ≥1 persisting NGS-detectable mutation. Compared with NGS-negative patients, NGS-positive patients had shorter overall survival (17 months versus median not reached; P = 0.004; hazard ratio = 2.2 [95% CI: 1.3-3.7]) and a shorter time to relapse (14 months versus median not reached; P = 0.014; HR = 1.9 [95% CI: 1.1-3.1]). Among 95 patients with a complete morphologic remission (CR), 43 (45%) were MRD-positive by NGS and 52 (55%) were MRD-negative. These MRD-positive CR patients had a shorter overall survival (16.8 months versus median not reached; P = 0.013; HR = 2.1 [95% CI: 1.2-3.9]) than did the MRD-negative CR patients. Post-treatment persisting MRD positivity, defined by the same NGS-based test used at diagnosis, is thus a more sensitive biomarker for low-level leukemic clones compared to traditional non-molecular methods and is prognostic of subsequent relapse and death.© 2023. The Author(s).