To Investigate The Factors Related With The Therapeutic Effect Of Primary Induction Chemotherapy Of Acute Myeloid Leukemia

Purpose and backgroud:Acute myeloid leukemia?AML?is a malignant disease of myeloid hematopoietic stem/progenitor cells.The abnormal proliferation of primary and immature myeloid cells of bone marrow and peripheral blood is the main feature.Anemia,fever,bleeding and other clinical manifestations occur because hematopoietic function of normal bone marrow is inhibited.Leukemia cells infiltrating peripheral tissues and organs results in enlargement of lymph nodes,liver splenomegaly,sternal tenderness,gingival hyperplasia and swelling,headache,vomiting,neck rigidity,convulsion and swelling of testis.The cell differentiation of AML is stagnant at an earlier stage,mostly for primordial cells and early immature cells.AML is highly malignant and progresses rapidly.Without normal treatment,the mean survival time is only about 3 months,and the short dies even after a few days of diagnosis.The treatment goal of AML is to completely remove the leukemia cells in the body and restore normal hematopoietic function.Chemotherapy is the main means to achieve this goal,which can be divided into two stages:induced remission and continuous treatment after remission.In 2010,the clinical guidelines for AML released by NCCN listed CEBPA,FLT3-ITD,NPM1 and C-KIT mutations as important prognostic indicators for AML.This article is intended to analyze the influence of genes,chromosomes,clinical features and laboratory tests,on the efficacy of primary induction chemotherapy in patients with AML?not APL?.Metheod:46 patients with definitive diagnosis of AML?not APL?were collected in China-Japan Union Hospital of Jilin University from May 2015 to January2018.Through the observation and analysis of the patients'age,gender,previous MDS/MPN history,presence of CNSL,the quantity of peripheral leukocytes at the initial diagnosis,prognostic risk,presence of mutations in the NPM1,c-kit/D816V and AML1/ETO,presence of double mutations in the CEBPA,SPSS 22.0 statistical software was used for statistical analysis and Log-Rank test was used to complete the univariate analysis of the remission of bone marrow after primary induction chemotherapy.Kaplan Meier was used to calculate survival rate and survival function,and plot the survivorship curve.COX regression model was used for multivariate analysis.We explore the influence of multiple factors on the remission of bone marrow after primary induction chemotherapy of AML?not APL?.Results:In this article 46 patients with AML?not APL?,19 cases were diagnosed as AML with maturation?AML-M₂?,11 cases were diagnosed as acute myelomonocytic leukemia?AML-M₄?,1 case was diagnosed as AML with eosinophilia?AML-M₄Eo?,15cases were diagnosed as acute monocytic leukemia?AML-M₅?.The ratio of male to female is 1.3:1.10 patients?21.7%?were older than or equal to 60 years old,36patients?78.3%?were younger than 60 years old,and the median age of onset was52 years old.1 case?2.2%?had CNSL.3 cases?6.5%?had MDS or MPN history,and 1case?2.2%?was treatment-related AML?after radiation therapy in spine?.CEBPA,c-kit/D816V,NPM1,FLT3-ITD and chromosome karyotype were detected in all patients.AML1/ETO was detected in 34 patients.32 cases were treated with IDA?idarubicin+Ara-C?for induction chemotherapy in 1 cycle.8 cases were treated with DA?daunorubicin+Ara-C?for induction chemotherapy in 1 cycle.1 case was treated with decitabine+Ara-C+aclarubicin for induction chemotherapy in 1 cycle.1 case was treated with decitabine plus HAG?homoharringtonine injection+granulocyte stimulating factor+Ara-C?for induction chemotherapy in 1 cycle.1 case was treated with CAG?aclarubicin+Ara-C+granulocyte stimulating factor?for induction chemotherapy in 1 cycle.1 case was treated with decitabine for induction chemotherapy in 1 cycle.1 case was treated with sequential induction chemotherapy with decitabine and homoharringtonine+Ara-C for induction chemotherapy in 1 cycle,and 1 case was treated with homoharringtonine+Ara-C for induction chemotherapy in 1 cycle.Bone marrow was re-examined during the myelosuppression or recovery period after chemotherapy.Among them,27 cases reached complete remission in bone marrow.12 cases reached partial remission in bone marrow and 7 cases were no remission in bone marrow.According to the grade of prognostic risk of patients of AML,22 cases in the good prognosis group,among them 20 cases?90.9%?achieved complete remission in bone marrow after 1 cycle of induction chemotherapy.17 cases in the medium prognosis group,among them 4 cases?23.5%?achieved complete remission in bone marrow after 1 cycle of induction chemotherapy.7 cases in the poor prognosis group,among them 3 cases?42.9%?achieved complete remission in bone marrow after 1cycle of induction chemotherapy.According to the quantity of peripheral leukocytes at the initial diagnosis,there were 4 patients with hyperleukocytosis?WBC?100×10⁹/L?,and among them 1 case?25%?achieved complete remission in bone marrow after 1 cycle of induction chemotherapy.NPM1 mutations were detected in 11 cases,and among them 8 cases?72.7%?reached complete remission in bone marrow after1 cycle of induction chemotherapy.CEBPA double mutations were detected in 6cases,and all of them?100%?reached complete remission in bone marrow after 1cycle of induction chemotherapy.C-kit/D816V mutations were detected in 4 cases,and none of them?0%?reached complete remission in bone marrow after 1 cycle of induction chemotherapy.9 cases were AML1/ETO positive,and among them 7 cases?77.8%?reached complete remission in bone marrow after 1 cycle of induction chemotherapy.8 cases had insertion mutations of FLT3-ITD,among them 6 cases?75%?reached complete remission in bone marrow after 1 cycle of induction chemotherapy.In univariate analysis,gender,MDS/MPN history,CNSL,treatment-related AML,mutations of NPM1,mutations of AML1/ETO and mutations of FLT3-ITD had no significant influence on the remission rate of primary induction chemotherapy.Whether there was hyperleukocytosis at the initial diagnosis,the grade of prognostic risk,whether there were double mutations in CEBPA and whether there were mutations in c-kit/D816V are the factors that influence on the efficacy of primary induction chemotherapy in patients with AML?not APL?,and P values are 0.011,0.001,0.035 and 0.002.In multivariate analysis,whether there were mutations in c-kit/D816V,whether there was hyperleukocytosis at the initial diagnosis,and the grade of prognostic risk are the factors that influence on the efficacy of primary induction chemotherapy,and P values are 0.006,0.001 and 0.021.Conclusion:1.It is of great significance to further explore the pathogenesis and clinical significance of changes in cytogenetics and molecular biology of AML for the improvement of the long-term survival rate and the realization of molecular targeting therapy.2.Univariate analysis shows that whether there is hyperleukocytosis at the initial diagnosis,the grade of prognostic risk,whether there are double mutations in CEBPA and whether there are mutations in c-kit/D816V are the factors that influence on the efficacy of primary induction chemotherapy in patients with AML?not APL?.The patients with no hyperleukopenia at the initial diagnosis,the prognosis risk graded as favourable prognosis,double mutations in CEBPA and no mutation in c-kit/D816V have high remission rate after primary induction chemotherapy.3.COX multivariate model analysis shows that whether there are mutations in c-kit/D816V,whether there is hyperleukocytosis at the initial diagnosis,and the grade of prognostic risk are the factors that influence on the efficacy of primary induction chemotherapy in patients with AML?not APL?.4.For patients with AML,the factors that affect the patients'prognosis should be fully considered,to guide the patients'treatment in a targeted way to achieve the best individualized therapeutic effect.