Analysis Of The Efficacy And Safety Of Decitabine Combined With Chemotherapy In Patients With Newly Diagnosed Acute Myeloid Leukemia

Objective:The purpose was to analyze the efficacy,safety and the related factors of decitabine combined with low-dose chemotherapy in patients with newly diagnosed acute myeloid leukemia.Methods:The eligible acute myeloid leukemia patients enrolled in First Hospital of Jinlin University were analyzed retrospectively from January 2014 to August 2016.All the patients suffered from the elderly(≥60 years),history of hematologic diseases,poor karyotypes,severe infections,organ dysfunction and other unfavorable factors.They were not given intensive therapy,and received decitabine combined with low-dose chemotherapy.Clinical characteristics,such as age,gender,gene mutations,fusion genes,karyotypes,peripheral white blood cell(WBC)counts and bone marrow(BM)blasts were collected.During the course of induction therapy,adverse events,including pathogenic infections,hematological toxicity and organ dysfunction were observed.Statistics were applied to evaluate the response rate,safety,prognosis and correlative factors.The Cut-off value of minimal residual disease(MRD)was explored by ROC curve and was used to assess the prognosis.According to the consolidation therapy,patients with CR or PR were divided into two groups(decitabine-based chemotherapy or not),in which the overall survival(OS)and disease free survival(DFS)were compared.Results:A total of 55 patients with newly diagnosed acute myeloid leukemia(AML)wereenrolled,the ratio of male to female was 24:31,the median age was 60 years(range,23~79 years).The median WBC counts at diagnosis was 3.31(range,0.53~54.53)×109/L,and the median BM blasts was 43.5%(range,19.0%~90.5%).Patients were classified with NCCN Guidelines(version 2016),incorporated 12 cases in low-risk group,27 cases in middle-risk group,and 16 cases in high-risk group AML.39 patients had at least 1 unfavorable factors(including the elderly,history of hematologic diseases,poor karyotypes and fusion genes),in which 30 patients with only 1 unfavorable factor,8 patients with 2 unfavorable factors,and 1 patient with 3or more unfavorable factors.Among these patients,47 cases were treated with DCAG,8 cases were induced by decitabine combined with other agents.The overall response rate(ORR)and complete remission(CR)rate were 80.0%(44/55)and 63.64%(35/55),respectively.Up to the deadline(October 1,2016),the survival rate was54.5%(30/55),the median overall survival(OS)and disease free survival(DFS)were17.0(13.7~20.3)months and 17.0(10.2~23.8)months,respectively.Univariate analysis suggested that ORR in different risk groups was different significantly(χ2=6.146,P=0.046).Our results also demonstrated that gender,age,gene mutations,WBC and BM blasts had no impact on response rate and OS(P>0.05).Multivariate analysis showed that the elderly(≥60 years)was the independent adverse prognostic factor for DFS.During the 21~28 days after induction therapy,the Cut-off value of minimal residual disease(MRD)was 1.34%.Patients with MRD ≥1.34% were inclined to have a shorter OS(P=0.056).In the patients with PR and above level,MRD ≥1.34%showed a significantly shorter OS than others(P=0.032).The level of MRD in patients who achieved CR had no association with OS(P=0.257),nevertheless,a shorter DFS was observed in patients with MRD ≥1.34%(P=0.043).Multivariate analysis showed that MRD ≥1.34% was the independent adverse prognostic factor for OS and DFS.Thirty-five patients achieved CR after one cycle of induction therapy.Among these patients,19 patients received one more decitabine-based chemotherapy,8patients received the other consolidation therapy directly,and 8 patients gave up.Ourstudy showed that patients with CR received an additional cycle of decitabine combined with chemotherapy had a significantly longer OS and DFS than others(P=0.025,P=0.017).A total of 44 patients achieved PR and above level,univariate analysis also showed that these patients benefited from an additional cycle of decitabine-based chemotherapy(P=0.026),nevertheless,a longer median OS was not observed in multivariate analysis.During the induction therapy,grade 4 hematological toxicity was commonly observed in 55 patients.The incidence of infection was 83.64%(46/55),and the incidence of severe infection(grade 3 to 4)was 18.18%(10/55).There were no serious damage on liver,kidney and cardiac function.The treatment-related mortality was 3.64%(2/55).Conclusions:1.Decitabine combined with low-dose chemotherapy was used for patients with newly diagnosed acute myeloid leukemia who were unfit for intensive chemotherapy,which showed a higher response rate and was well tolerated.2.After induction therapy,patients with MRD≥1.34% suggested a shorter OS than the others.3.Patients with CR received an additional cycle of decitabine combined with chemotherapy showed a longer OS and DFS.