二代测序检测克隆性基因突变对RUNX1-RUNX1T1阳性急性髓系白血病的预后价值

OBJECTIVE: To investigate the prognostic value of clonal gene mutations detected by second-generation sequencing in patients with positive RUNX1-RUNX1T1 acute myeloid leukemia （AML） who received high-dose chemotherapy or autologous transplantation （intensive consolidation therapy）in the first complete remission（CR(1)）state. METHODS: 79 AML patients with positive RUNX1-RUNX1T1 who received intensive consolidation therapy in CR(1) state from July 2011 to August 2017 were analyzed retrospectively. Kaplan-Meier curve and Cox regression model were used to figure out the effect of leukocyte counts at onset and gene mutations for prognosis. RESULTS: C-KIT, FLT3, CEBPA and DNMT3A gene mutations were found in 25（31.6％）, 6（7.6％）, 7（8.9％）and 1（1.3％）patient among the population. Mutations in C-KIT exon17 and C-KIT exon8 were detected in 19（24.1％）and 5（6.3％）cases, respectively, and mutations of FLT3-ITD were confirmed in 5（6.3％）cases. The higher leukocyte counts presented at onset of leukemia, the shorter overall survival（OS）was seen in these patients（P＝0.03）. Patients with C-KIT exon17 mutation had significantly shorter OS（P＝0.01）and disease free survival（DFS）（P＝0.006）compared with those without gene mutations, and patients with FLT3-ITD gene mutation got the inferior OS（P＝0.048） and DFS （P＝0.071）. CONCLUSION: In AML patients with positive RUNX1-RUNX1T1 receiving intensive consolidation therapy, the white blood cell counts at onset of leukemia, C-KIT mutations in exon 17, and FLT3-ITD gene mutations suggest poor prognosis, which would contribute to elaborate risk stratification, personalized treatment and predict prognosis for these patients.