The Analysis Of Clinical Efficacy Of Decitabine Combined With CAG Regimen In Treatment Of Elderly And Refractory/Relapsed Acute Myeloid Leukemia

Objective:To investigate the clinical efficacy and safety of decitabine combined with CAG regimen treatment for patients with elderly and refractory/relapsed acute myeloid leukemia (AML) or AML transformed from myelodysplastic syndrome/ myeloproliterative neoplasms.Additionally,to explore the expression of DNA methyltransferase 3A(DNMT3A mRNA) mRNA in bone marrow aspirate before treatment,to discuss the molecular mechanism of DNMT3A mRNA as choice indicator, to provide foundation for prediction model.Methods:The clinical data of 18 patients with elderly and refractory/relapsed acute myeloid leukemia (AML) or AML transformed from myelodysplastic syndrome/ myeloproliterative neoplasms enrolled from January 2012 to April 2O16.They were given decitabine combined with CAG regimen. The expression of DNMT3A mRNA was detected by RT-PCR in 16 cases bone marrow aspirate pretreatment.Results:1.Up to April 1st 2016, Among 18 patients treated by decitabine combined chemothe-raphy procotol, overall response rate is 72.2%,10(55.6%) achieved complete remission,2(11.1%) achieved CR with incomplete peripheral blood count recovery,1(5.5%) partial remission,5 (27.8%) no response,9 patients still survival,5 got remission with no evidence of disease,9 died,the median overall survival was 13 months (1-20M).2.Decitabine combined chemotheraphy procotol mainly caused hematological adverse events as myelosuppression, less nonhematologic adverse events. Grade 3 to 4 hematological toxicities were observed in all 18patients(100%),the average time for lack of neutrophil cells was 22.61±4.54d, the average time of thrombocytopenia was 16.06±3.91d, the average dose of red blood cell and platelet transfusion were 6.17± 4.85U、32.5±19.5U,72.2% and 22.2% patients experienced grade 3 to 4 pneumonia and mucosa or soft tissue infection,22.2% was 1 to 2 grade bleeding,16.7% was 1 to 2 grade hepatic injury,5.6% was 3 to 4 grade hepatic injury,6.1% was 1 to 2 gastroin-testinal adverse reactions.3.They were no statistically significant differences outcomes in clinicopathologic factors such as age、sex、course of disease、risk stratification、classification of type、 bone marrow blast cell counts before treatment(P>0.05).The differences of clinical outcomes among onset peripheral white blood cell counts were statistically signifi-cant(P=0.038).To compare two respectively,CR group and NR group difference was statistically significant,there was no statistically significant between the remaining groups.4.To compare the expression of pretreatment bone marrow DNMT3A mRNA, responders also had a trend for lower levels of DNMT3A mRNA compared with nonrespond ers (P=0.002).Conclusions:1.The decitabine combined with CAG regimen produced high efficacy and well be tolerated.2. The treatment regimen is more suitable for AML with less peripheral white blood cell counts. Different factors such as age、sex、course of disease、risk stratification、 classification of type、onset bone marrow blast cell counts were no statistically significant differences in clinical outcomes.3. We identified lower pretreatment levels of DNMT3A mRNA were associated with achievement of better clinical response with Decitabine combined chemotheraphy. The findings support the expression of DNMT3A mRNA used as a molecular indicators for the treatment regimen selection.