Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion: AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.
目的： 探讨FLT3-ITD和DNMT3A R882双突变对急性髓系白血病（AML）患者allo-HSCT预后的影响。 方法： 使用直接测序法检测206例接受allo-HSCT的AML患者（M(3)和使用分子靶向药物索拉菲尼的病例除外）初诊时骨髓中常见的基因突变组套（包括FLT3-ITD、DNMT3A、c-kit、CEBPA、FLT3-TKD、NPM1），回顾性分析患者的临床资料，比较各基因突变组的移植预后。 结果： ①206例AML患者中男104例，女102例，中位年龄38（3~63）岁。FAB分型：M(0) 6例，M(1) 24例，M(2) 56例，M(4) 39例，M(5) 63例，M(6) 6例，不能分类12例。②全部206例患者根据初诊时的突变基因情况分为4组：FLT3-ITD(+) DNMT3A R882(+)组（A组）19例，FLT3-ITD(+) DNMT3A R882(－)组（B组）38例，FLT3-ITD(－)DNMT3A R882(+)组（C组）21例，FLT3-ITD(－)DNMT3A R882(－)组（D组）128例。四组间性别、年龄、初诊时白细胞计数、FAB分型、移植前疾病状态、染色体核型、供者类型、预处理方案及GVHD发生率比较，差异无统计学意义（P>0.05）。③A组和B、C、D组比较，2年累积复发率较高[分别为（72.2±2.6）%、（38.6±0.6）%、（36.8±1.6）%、（27.8±0.1）%，P值均<0.05]，总生存率较低[分别为（30.9±13.3）%、（67.5±7.8）%、（61.4±12.4）%、（80.1±3.7）%，P值均<0.05]，无白血病生存率较低[分别为（11.3±10.2）%、（47.9±8.4）%、（56.8±12.5）%、（79.7±3.6）%，P值均<0.05]。 结论： 伴有FLT3-ITD与DNMT3A R882双突变的AML患者移植后累积复发率较高，总生存率和无白血病生存率较差。.
Keywords: DNMT3A R882 mutation; FLT3-ITD mutation; Hematopoietic stem cell transplantation; Leukemia, myeloid, acute.