Clinical Study Of Decitabine Combined With CAG Regimen In Acute Myeloid Leukemia

Objective:Acute myeloid leukemia(AML)is the most common acute leukemia diagnosed in adult patients,over 50%were older patients.Elder patients with AML have significant comorbities,lower complete remission rate and poorer prognosis.In recent years,the hypomethylating agent decitabine(DAC)has been used in elderly MDS and AML patients with a certain therapeutic effect.Recent studies suggested haploidentical lymphocyte infusion(HLI)played a promising role in treating AML.Therefore,we initiated a multicenter,single-arm,prospective clinical trial:DAC combined with modified CAG regimen followed by haploidentical lymphocyte infusion for newly diagnosed older AML patient.The aim was to evaluate the clinical efficacy and adverse effects of this regimen.Methods:Screening untreated older AML patients since April 2012 according to the inclusion and exclusion critira.The patients were enrolled the clinical trial after signing the informed consent form.Treatment design:decitabine(20 mg/m2,intravenously for 5 days),aclacinomycin(ACM,20mg every second day intravenously for 5 days),cytarabine(10 mg/m2 every 12 hours subcutaneously for 5 days),granulocyte colony-stimulating factor(G-CSF,300 ?g/day subcutaneously from day 0 to neutrophil recovery)and a combination with HLI.Haploidentical lymphocyte infusionwere administered 36 hours after the final dose of chemotherapy.Clinical data were collected,the clinical characteristics?CR rate?survival and adverse effects were analyzed.Results:There were 29 patients with previously untreated AML defined by World Health Organization(WHO)criteria enrolled in the study,including 10 women and 19 men.The median age of these patients was 64(range 57-77).The median white blood cell(WBC)count was3.78(0.74-228.28)× 109/L.The median bone marrow blast count was 60%(20.6%-95%).10 subjects with poor-risk,19 subjects with intermediate-risk.Number of patients with ECOG 1,2,3 was 5,12,12 respectively.The median treatment cycle is 3(1-4),16 achieved complete remission(CR)and 9 achieved partial remission(PR)after the first treatment cycle.Of the patients with PR,5 subjects achieved CR after the second induction,which brings the overall CR rate to 72.1%.1-year overall survival(OS)and 2-year OS was 72.2%and 35%,1-year DFS and 2-year DFS was 54.5%and 24.5%respectively.CR rate in different age,ECOG,risk status,WBC and bone marrow blast cell were no significant difference.OS was significantly longer in patient with WBC<20×109/Lat diagnosis,and OS was significantly longer in patient with intermediate risk than poor risk.All patients tolerant well with this therapy,mainly adverse effect was neutropenia and thrombocytopenia,the media time of neutrophil and platelet recovery was 11 and 14 day.Only one patient(3.4%)died of lung infection in 8 weeks.Conclusion:Decitabine combined with modified CAG regimen followed by haploidentical lymphocyte infusion for elderly patients with acute myeloid leukemia is a safe and effective induction therapy.OS was longer in patient with lower WBC and risk status.Objective:Acute myeloid leukemia(AML)is the most common acute leukemia diagnosed in adult patients,with a median age of 65years at diagnosis.In recent years,with the development of chemotherapy and hematopoietic stem cell transplantation,remission rate and overall survival in acute myeloid leukemia were improved.But there are still some patients cannot obtain complete remission,or even still relapse after complete remission.For elder and relapse and refractory patients with AML can't tolerant intensive chemotherapy because of significant comorbities and poorer ECOG.In recent years,the demethylation drug decitabine(DAC)has been used in relapse and refractory AML,but the effect was not satisfied.We use decitabine combied modified CAG regimen treated a set of relapse and refractory patients,retrospective analyze the clinical data and aim to evaluate the clinical efficacy and safety.Methods:Retrospective analyzed 43 relapse and refractory AML patients receiveing decitabine combined modified CAG regemin from April 2012 to December 2015.Treatment design:decitabine(20 mg/m2intravenously for 5 days),aclacinomycin(ACM,20mg every second day intravenously for 5 days),cytarabine(100 mgevery 12 hours subcutaneously for 5 days),granulocyte colony-stimulating factor(G-CSF,300?g/day subcutaneously from day 0 to neutrophil recovery.Clinical data were collected,and analyzing the clinical characteristics?CR rate?survival and adverse effects.Results:43repalse and refractory AML patients were analyzed,including 14 women and 29 men.The median age of these patients was 45(range 19-76),1 patient with extramedullary relapse,8 patients relapsed after transplantation.17 patients was refractory AML,16 patients was refractory AML,previous median number of courses in these patients was 3(1-20)and 10 patients failed to achieve complete remission after 1 cycle standerd chemotherapy.30 patients with ECOG ?2,9 patient with favorable risk,18 with intermediate risk,13 with poor risk and 3 not available by NCCN categories.The median white blood cell count was3.27(0.61-295.18)×109/L.The median bone marrow blast count was 61.2%(8%-92%).21 achieved CR after the first cycle,CR rate was 48.8%.Of the patients with PR,3 patients achieved CR and of the patient with NR,2 patients achieved CR after the second induction5 which brings the overall CR rate to 60.5%.CR rate in favorable and intermediate risk was superior to in poor risk,CR rate in ECOG 1-2 was superior to in ECOG 3(p=0.030.0.022.0.047).1 year OS in all patients was 64.9%,1 year DFS was 48.1%.Univariate analyses show CR.transplantation.ECOG and risk status were associated with OS.Multivariate analyses show OS in patients with transplantation and good ECOG was sinificanty longer(p=0.018.0.003)· ALL patients can tolerant this regimen,mainly adverse effect was neutropenia and thrombocytopenia,the media time of neutrophil and platelet recovery was 18 and 20 day.4 patient(9.2%)died in 8 weeks,2 died of disease progression and 2 died of infection.Conclusion:Decitabine combined with modified CAG regimen for relapse and refractory patients with acute myeloid leukemia is a safe and effective regimen.CR rate was better in lower risk status and good ECOG,OS was longer in patients with transplantation and good ECOG.