The Prognostic Significance Of Molecular Genetic Combined With Bone Marrow Examination In Cytogenetically Normal Acute Myeloid Leukemia

Objective:To investigate the prognosis rules by combining the NPM1 and FLT3 gene mutations with the bone mararow examination at the end of induction chemotherapy(T time point) in cytogenetically norml-Acute myeloid leukemia patients, looking for a new model to judge the prognosis of AML.Methods:The data of 100 CN-AML patients(non M3) hosipitalized from January, 2010 to January, 2014 were retrospective reviewed. The enrolled patients were received bone marrow aspirates at the end of induction chemotherapy and during myelosuppression phase.The prognosis of CN-AML patients was analyzed according to the molecular genetics(FLT3 and NPM1 gene status) and the percentage of residual bone marrow blasts at T time point or during myelosuppression phase.Results:1 After analysising the FLT3 and NPM1 gene respectively. In FLT3+ group, the complete remission(CR) rate was 13.9%, 2 yesrs RFS rate was 5.6%, 2 yesrs OS rate was19.4%, the median time of relapse-free survival(RFS) and overall survival(OS) were 6.9and 9.4 months. The difference was significant between FLT3+ and FLT3-(P<0.001), but the difference between NPM1+ and NPM1- group didn’t have statistically significant(P>0.05).2 Patients were divided into four subgroups by the NPM1 and FLT3 gene mutations,NPM1+/FLT3-, NPM1-/FLT3-, NPM1-/FLT3+ and NPM1+/FLT3+. The prognosis of patients in NPM1+/FLT3- group was the best. The NPM1-/FLT3+ group had similar CR, FRS and OS with the NPM1+/FLT3+ group. The NPM1+/FLT3- group was called good prognosis group, NPM1-/FLT3- was called intermediate prognosis group, NPM1-/FLT3+ and NPM1+/FLT3+ were called poor prognosis group.3 Patients were divided into two subgroups by a cutcoff 5% residual bone marrow blasts at T time point and during myelosuppression phase. Patients with percentage of residual bone marrow blasts cell<0.05 had better prognosis than the patients with percentage≥0.05 at T time point or during myelosuppression phase. The percentage of residual bone marrow blast cells at T time point was correlated with that during myelosuppression phase.4 CN-AML patients were analysed by combining molecular genetic with bone marrow examination at T time point. The prognosis of patients in the C group(imtermediate group+<0.05) had similar CR, FRS, OS with the NPM1+/FLT3- patients.The E group(poor group+<0.05) had similar CR, FRS, OS with the D group(imtermediate group +≥0.05). And the F group had the worst prognosis.5 COX regression analysis showed that the FLT3 gene and the percentage of residual bone marrow blasts at T are independent prognostic factors of CN-AML. NPM1 is an independent prognostic factor of FLT3- patients.Conclusion:The molecular genetic can be used for the risk-stratification of CN-AML patients,which is helpful to guide the selection of clinical programs; According to the percentage of residual bone marrow blasts at T time point, we can evaluate the chemotherapy reactivity and sensitivity of CN-AML patients early and objectively, and a better further treatment strategie can be designed; FLT3 gene and the percentage of residual bone marrow blasts at T time point are independent prognostic factors of CN-AML. NPM1 is an independent prognostic factor of FLT3- patients.