The Clinical Characteristics And Prognosis Of Acute Myeloid Leukemia Patients With CEBPA Mutations

Objective：The purpose of this study was to analyze the incidence rate of CEBPAmutations of the newly diagnosed of acute myeloid leukemia (AML) patients,and to evaluate the clinical characteristics, therapeutic response, and long-termoutcome.Methods:Total208patients of the newly diagnosed acute myeloid leukemia, fromThe First Hospital of Jilin University, during between August,2011to August,2011, were retrospectively analyzed. All patients were diagnosed by MICM.One hundred and six cases were male, and102cases were female, the medianage of47.5years (ranged from7to80years). CEBPA, NPM1, FLT3-ITDmutation status was detected using polymerase chain reaction (PCR). Theclinical data of the patients, such as age, gender, peripheral blood leukocyte,hemoglobin, platelet, the proportion of primitive bone marrow cells and so on,were collected. The induction therapy mainly used standard doses of DA, IA ordecitabine combined with CAG. After induction relief, the patients receivedhigh-dose cytarabine and consolidated for3~4courses, and maintainedtreatment of DA, MA for3~4courses. The clinical characteristics of thepatients with CEBPA double mutated were compared with these of no CEBPAmutated patients, and evaluated the therapeutic response and long-termoutcome of the patients with CEBPA double mutations. Results:In208patients in this study, CEBPA mutations were detected in37patients(17.8%),29cases (13.95%) were double mutations,8cases (3.85%) weresingle mutation among37cases. In117patients with normal karyotype,28cases (23.9%) were found with CEBPA mutations, with22cases (18.8%) weredouble mutations. As compared with no CEBPA mutation, the followingcharacteristics were observed in patients with CEBPA double mutations:presented with younger age at diagnosis (P=0.021);82.8%of the patients wereM1and M2; presented with higher peripheral white blood cell count ([23.71(8.53,94.90)]×109/L vs.[9.75(3.13,43.51)]×109/L; u=2.736, P=0.006)、higherhemoglobin ([91.38±22.36]×g/L vs.[76.87±23.70]×g/L; t=3.037, P=0.002),lower platelet count ([21.0(12.0,43.5)]×109/L vs.[41.0(21.0,78.0)]×109/L;u=3.441, P=0.001); CD7、CD34and HLA-DR expression was upregulated atdiagnosis and differences were statistically significant (all P<0.05). There wereno statistical significant (P>0.05) in the sex; the percentage of primitive bonemarrow cells; CD15expression; the incidence of NPM1、FLT3-ITD mutation inthe two groups of patients. One hundred and sixty patients received inductiontreatment,127cases were evaluated. After1-2course induction therapy,110patients (86.7%) achieved complete remission. All of23patients (100%) withCEBPA double mutations got complete remission; in104patients with noCEBPA mutation,87cases (83.7%) achieved complete remission. The completeremission rates in patients with CEBPA double mutations were better than thesein patients with no CEBPA mutation (P=0.041). There were97patients whowere received high-dose cytarabine consolidated1courses at least enrolled thesurvival analysis. Follow-up time ranged2to34months, the median follow-uptime was10months. Thirty patients (30.9%) were relapsed. In21patients withCEBPA double mutations,5cases (23.8%) were relapsed; in76patients with noCEBPA mutation,25cases (32.9%) were relapsed, but there was no statisticalsignificant (P=0.425). All of12dead patients had no CEBPA mutation. The relapse-free survival of patients with CEBPA double mutation was marginallybetter than that of patients with no CEBPA mutation, but no statisticalsignificance was found (RFS2years:64.6%vs.58.2%, P=0.318). As comparedwith no CEBPA mutation, the patients with CEBPA double mutations had betteroverall survival （2-years OS:100%vs.75.1%; P=0.045）.Conclusions:As compared with that reported in abroad, the incidence rate of CEBPAmutations was slightly higher in patients with AML. The patients with CEBPAdouble mutation frequently found in normal karyotype and the patients havecertain clinical characteristics. The complete remission rates and the overallsurvival of patients with CEBPA double mutations were better than these ofpatients with no CEBPA mutations. CEBPA double mutations were one ofindicators of favorable prognosis.