Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia.
Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia.
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DOI：
10.1001/jama.2015.9643
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发表时间：
2015-08-25
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影响因子：
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通讯作者：
Ley TJ
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作者：
Klco JM;Miller CA;Griffith M;Petti A;Spencer DH;Ketkar-Kulkarni S;Wartman LD;Christopher M;Lamprecht TL;Helton NM;Duncavage EJ;Payton JE;Baty J;Heath SE;Griffith OL;Shen D;Hundal J;Chang GS;Fulton R;O'Laughlin M;Fronick C;Magrini V;Demeter RT;Larson DE;Kulkarni S;Ozenberger BA;Welch JS;Walter MJ;Graubert TA;Westervelt P;Radich JP;Link DC;Mardis ER;DiPersio JF;Wilson RK;Ley TJ
预测急性髓性白血病（AML）患者预后的测试是不精确的，特别是对于那些中度风险的AML患者。确定基因组方法是否可以为成年新生AML患者提供新的预后信息。对71例AML患者（平均年龄50.8岁）在疾病表现时获得的样本进行全基因组或外显子组测序，这些患者于2002年3月开始在单一地点接受标准诱导化疗，随访至2015年1月。此外，在诱导治疗成功后约30天，对来自50例患者（包括32例中度风险AML）的配对诊断和缓解样本进行深度数字测序。50名患者中有25名来自71名患者，25名是新增病例。全基因组或外显子组测序和靶向深度测序。基于遗传数据的识别风险。突变模式（包括化疗后白血病相关变异的清除）及其与无事件生存期和总生存期的关系。对71例患者的全面基因组数据的分析并没有改善目前标准治疗指标的结果评估。在一项对50名患者的分析中，有报告和记录的缓解样本，24名（48%）患者在缓解时至少有5%的骨髓细胞存在持续的白血病相关突变。与清除所有突变的26名患者相比，24名持续突变患者的无事件生存率和总生存率显著降低。中等细胞遗传风险的患者也有类似的发现。在30天缓解样本中，至少5%的骨髓细胞中检测到持续的白血病相关突变，与复发风险显著增加和总生存期降低相关。这些数据表明，这种基因组方法可以改善AML患者的风险分层。
Tests that predict outcomes for patients with acute myeloid leukemia (AML) are imprecise, especially for those with intermediate risk AML. To determine whether genomic approaches can provide novel prognostic information for adult patients with de novo AML. Whole-genome or exome sequencing was performed on samples obtained at disease presentation from 71 patients with AML (mean age, 50.8 years) treated with standard induction chemotherapy at a single site starting in March 2002, with follow-up through January 2015. In addition, deep digital sequencing was performed on paired diagnosis and remission samples from 50 patients (including 32 with intermediate-risk AML), approximately 30 days after successful induction therapy. Twenty-five of the 50 were from the cohort of 71 patients, and 25 were new, additional cases. Whole-genome or exome sequencing and targeted deep sequencing. Risk of identification based on genetic data. Mutation patterns (including clearance of leukemia-associated variants after chemotherapy) and their association with event-free survival and overall survival. Analysis of comprehensive genomic data from the 71 patients did not improve outcome assessment over current standard-of-care metrics. In an analysis of 50 patients with both presentation and documented remission samples, 24 (48%) had persistent leukemia-associated mutations in at least 5%of bone marrow cells at remission. The 24 with persistent mutations had significantly reduced event-free and overall survival vs the 26 who cleared all mutations. Patients with intermediate cytogenetic risk profiles had similar findings. The detection of persistent leukemia-associated mutations in at least 5%of bone marrow cells in day 30 remission samples was associated with a significantly increased risk of relapse, and reduced overall survival. These data suggest that this genomic approach may improve risk stratification for patients with AML.