文章：

FLT3-ITD和NPM1突变对复发急性髓性白血病患者预后的影响及中危细胞遗传学

The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics

原文发布日期：2013-05-24

DOI: 10.1038/bcj.2013.14

类型: Original Article

开放获取: 是

英文摘要：

Internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis, but less is known about their utility to predict outcomes at relapse. We retrospectively analysed outcomes of 70 patients with relapsed, intermediate-risk karyotype AML who received a uniform reinduction regimen, with respect to FLT3-ITD and NPM1 mutation status and first complete remission (CR1) duration. CR1 duration, but not molecular status, was significantly correlated with CR2 rate. On univariate analysis, patients with mutated FLT3-ITD (FLT3+) had significantly worse overall survival (OS) compared with those with neither an NPM1 nor FLT3-ITD mutation (NPM1-/FLT3-). On multivariate analysis, shorter CR1 duration was significantly correlated with inferior OS at relapse (P<0.0001), while FLT3 and NPM1 mutation status and age were not significantly correlated with OS. Patients who subsequently underwent allogeneic stem cell transplant (alloSCT) had a superior OS regardless of CR1 duration, but outcomes were better in patients with CR1 duration>12 months. In intermediate-risk karyotype AML patients receiving reinduction, CR1 duration remains the most important predictor of OS at relapse; FLT3-ITD and NPM1 status are not independent predictors of survival.

摘要翻译： 

fms样酪氨酸激酶-3基因内部串联重复（FLT3-ITD）和核仁磷酸蛋白-1（NPM1）突变对初诊时具有中等风险核型的急性髓系白血病（AML）患者具有预后意义，但关于这些突变在预测复发结局方面的作用尚不明确。我们回顾性分析了70例接受统一再诱导治疗方案的复发中等风险核型AML患者的结局，评估指标包括FLT3-ITD与NPM1突变状态及首次完全缓解（CR1）持续时间。结果显示CR1持续时间（而非分子状态）与二次完全缓解（CR2）率显著相关。单变量分析表明，与无NPM1或FLT3-ITD突变（NPM1-/FLT3-）的患者相比，FLT3-ITD突变（FLT3+）患者的总生存期（OS）显著更差。多变量分析显示，较短的CR1持续时间与复发时较差的OS显著相关（P<0.0001），而FLT3与NPM1突变状态及年龄与OS无显著相关性。后续接受异基因干细胞移植（alloSCT）的患者无论CR1持续时间如何均具有更优的OS，但CR1持续时间>12个月的患者结局更佳。在接受再诱导治疗的中等风险核型AML患者中，CR1持续时间仍是复发时OS最重要的预测指标；FLT3-ITD和NPM1状态并非独立的生存预测因子。

原文链接：

The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics