Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies those at high risk of relapse
Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies those at high risk of relapse
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DOI：
10.3324/haematol.2014.104133
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发表时间：
2014-08-01
期刊：
影响因子：
10.1
通讯作者：
Spiekermann, Karsten
中科院分区：
文献类型：
--
作者：
Hubmann, Max;Koehnke, Thomas;Spiekermann, Karsten
监测微小残留病是识别复发高危急性髓系白血病患者的重要途径。在这项研究中，我们通过对AMLCG 1999年、2004年和2008年试验中接受治疗的患者进行NPM 1突变的实时定量聚合酶链反应分析，研究了微小残留病监测的预后潜力。在再生障碍、诱导治疗后、巩固治疗后和随访期间，对来自158名NPM 1突变A、B和D阳性患者的588份样本进行了监测（灵敏度为10（-6））。127例患者（80.4%）在诱导治疗后达到完全缓解，其中56例患者（44.1%）复发。在每个检查点，计算最小残留疾病临界值。诱导治疗后，截止NPM 1突变率为0.01与4.26的高风险比和76%的预测复发的最高灵敏度相关。这反映在比率高于临界值的患者2年后复发的累积发生率为77.8%，而比率低于临界值的患者为26.4%。在根据European LeukemiaNet的有利亚组中，诱导治疗后的截止值也将队列分为两个预后组，2年后复发的累积发生率为76%与6%。我们的数据表明，除了治疗前因素外，个体的微小残留疾病病程也是一个重要的预后因素，可以纳入临床试验中，以指导缓解后治疗。
Monitoring minimal residual disease is an important way to identify patients with acute myeloid leukemia at high risk of relapse. In this study we investigated the prognostic potential of minimal residual disease monitoring by quantitative real-time polymerase chain reaction analysis of NPM1 mutations in patients treated in the AMLCG 1999, 2004 and 2008 trials. Minimal residual disease was monitored - in aplasia, after induction therapy, after consolidation therapy, and during follow-up - in 588 samples from 158 patients positive for NPM1 mutations A, B and D (with a sensitivity of 10(-6)). One hundred and twenty-seven patients (80.4%) achieved complete remission after induction therapy and, of these, 56 patients (44.1%) relapsed. At each checkpoint, minimal residual disease cut-offs were calculated. After induction therapy a cut-off NPM1 mutation ratio of 0.01 was associated with a high hazard ratio of 4.26 and the highest sensitivity of 76% for the prediction of relapse. This was reflected in a cumulative incidence of relapse after 2 years of 77.8% for patients with ratios above the cut-off versus 26.4% for those with ratios below the cut-off. In the favorable subgroup according to European LeukemiaNet, the cut-off after induction therapy also separated the cohort into two prognostic groups with a cumulative incidence of relapse of 76% versus 6% after 2 years. Our data demonstrate that in addition to pre-therapeutic factors, the course of minimal residual disease in an individual is an important prognostic factor and could be included in clinical trials for the guidance of post-remission therapy.