文章：

核磷蛋白突变在869例儿童急性髓系白血病患者中具有独立的有利预后影响

Nucleophosmin mutations confer an independent favorable prognostic impact in 869 pediatric patients with acute myeloid leukemia

原文发布日期：2020-01-09

DOI: 10.1038/s41408-019-0268-7

类型: Article

开放获取: 是

英文摘要：

Studies on the clinical significance of Nucleophosmin (NPM1) mutations in pediatric AML in a large cohort are lacking. Moreover, the prognosis of patients with co-occurring NPM1 and FLT3/ITD mutations is controversial. Here, we analyzed the impact of NPM1 mutations on prognoses of 869 pediatric AML patients from the TAGET dataset. The frequency of NPM1 mutations was 7.6%. NPM1 mutations were significantly associated with older age (P < 0.001), normal cytogenetics (P < 0.001), FLT3/ITD mutations (P < 0.001), and high complete remission induction rates (P < 0.05). Overall, NPM1-mutated patients had a significantly better 5-year EFS (P = 0.001) and OS (P = 0.016) compared to NPM1 wild-type patients, and this favorable impact was maintained even in the presence of FLT3/ITD mutations. Stem cell transplantation had no significant effect on the survival of patients with both NPM1 and FLT3/ITD mutations. Multivariate analysis revealed that NPM1 mutations were independent predictors of better outcome in terms of EFS (P = 0.004) and OS (P = 0.012). Our findings showed that NPM1 mutations confer an independent favorable prognostic impact in pediatric AML despite of FLT3/ITD mutations. In addition, pediatric AML patients with both NPM1 and FLT3/ITD mutations appear to have favorable prognoses and may not need hematopoietic stem cell transplantations.
 

摘要翻译： 

目前尚缺乏大规模队列研究探讨核仁磷酸蛋白（NPM1）突变在儿童急性髓系白血病（AML）中的临床意义。此外，同时存在NPM1与FLT3/ITD突变患者的预后存在争议。本研究通过TAGET数据集分析了NPM1突变对869例儿童AML患者预后的影响。NPM1突变发生率为7.6%，其与较高年龄（P＜0.001）、正常核型（P＜0.001）、FLT3/ITD突变（P＜0.001）及高完全缓解诱导率（P＜0.05）显著相关。总体而言，与NPM1野生型患者相比，NPM1突变患者的5年无事件生存率（P=0.001）和总生存率（P=0.016）显著更优，且这种积极影响在合并FLT3/ITD突变时仍然存在。干细胞移植对同时携带NPM1与FLT3/ITD突变患者的生存率无显著改善。多变量分析显示，NPM1突变是改善无事件生存率（P=0.004）和总生存率（P=0.012）的独立预测因子。本研究结果表明，在儿童AML中，NPM1突变具有独立的良好预后影响，且不受FLT3/ITD突变干扰。此外，同时携带NPM1与FLT3/ITD突变的儿童AML患者预后良好，可能无需进行造血干细胞移植。

原文链接：

Nucleophosmin mutations confer an independent favorable prognostic impact in 869 pediatric patients with acute myeloid leukemia