DNMT3A、FLT3-ITD合并NPM1基因突变正常核型急性髓系白血病患者的临床特征及预后分析

目的 分析DNMT3A、FLT3-ITD合并NPM1基因突变的正常核型急性髓系白血病(AML)患者的临床特征,探讨该类患者的预后.方法 回顾性分析2005年12月至2014年6月就诊的109例正常核型AML患者的临床特征及预后.其中DNMT3A/FLT3-ITD/NPM1+AML患者共25例,单独FLT3-ITD+ AML患者共32例,单独NPM1+AML患者24例,单独DNMT3A+ AML患者28例.结果 25例DNMT3A/FLT3-ITD/NPM1+ AML患者平均年龄46岁,伴有高白细胞(81.7×109/L)及较高的骨髓原始细胞(66.3％).其中,17例选择大剂量化疗,8例行异基因造血干细胞移植,与DNMT3A+、FLT3-ITD+、NPM1+AML组比较,差异均无统计学意义.25例DNMT3A/FLT3-ITD/NPM1+患者的3年总生存率为17.65％,3年无病生存率为13.88％,与DNMT3A+、FLT3-ITD+、NPM1+AML组差异均有统计学意义(P值分别为0.049 9、0.036 1、0.013 4),3年无病生存率差异无统计学意义(均P＞ 0.05).结论 DNMT3A、FLT3-ITD合并NPM1基因突变的正常AML患者往往合并高的外周血白细胞及骨髓原始细胞,预后较差.

Clinical characteristics and prognostic analysis of cytogenetically normal acute myeloid leukemia patients with DNMT3A,FLT3-ITD and NPM1 mutations

Objective To analyze clinical characteristics of cytogenetically normal acute myeloid leukemia (CN-AML) patients with DNMT3A, FLT3-ITD and NPM1 mutations (DNMT3A/FLT3-ITD/NPM1+),and explore the prognosis of these patients.Methods The clinical characteristics and prognosis of 109 CN-AML patients in our center from Dec 2005 to Oct 2014 were retrospectively analyzed.Based on gene mutations, these patients were divided into 4 groups: DNMT3A/FLT3-ITD/NPM1+ AML patients (n =25), FLT3-ITD+ AML patients (n =32), NPM1+ AML patients (n =24), DNMT3A+ AML patients (n =28).Results The average age of 25 DNMT3A/FLT3-ITD/NPM1 + patients was 46 years old, including 9 males and 16 females.Higher white blood cells (81.7×l09/L) and bone marrow blasts (66.3 ％) were found in DNMT3A/ FLT3-ITD/NPM1+ group.The 3 years overall survival (3-OS) rate and 3 years disease free survival (3-DFS) rate in DNMT3A/FLT3-ITD/NPM1+ group were 17.65 ％ and 13.88 ％, respectively.In DNMT3A/FLT3-ITD/NPM1+ group, 17 patients received chemotherapy as consolidation therapy, and 8 patients received allogeneic hematopoietic stem cell transplantation (HSCT).There were significant differences in 3-OS between DNMT3A/ FLT3-ITD/NPM1+ group and FLT3-ITD+ group, NPM1+ AML group or DNMT3A+ group (DNMT3A+ group: P =0.049 9, FLT3-ITD+ group: P =0.036 1, NPM1 + group: P =0.013 4), while no differences in 3-DFS were found (P ＞ 0.05).Conclusions There are higher white blood cells and bone marrow blasts in DNMT3A/ FLT3-ITD/NPM1+ CN-AML patients compared with those in FLT3-ITD+, NPM1+ AML or DNMT3A+ patients.DNMT3A/FLT3-ITD/NPM1+ CN-AML patients likely have the poor survival.