The hypomethylating agent decitabine prior to chemotherapy improves the therapy efficacy in refractory/relapsed acute myeloid leukemia patients

// Xuejie Jiang 1 , Zhixiang Wang 1 , Bingjie Ding 1 , Changxin Yin 1 , Qingxiu Zhong 1,2 , Bing Z. Carter 3 , Guopan Yu 1 , Ling Jiang 1 , Jieyu Ye 1 , Min Dai 1 , Yu Zhang 1 , Shuang Liang 4 , Qingxia Zhao 5 , Qifa Liu 1 and Fanyi Meng 1,2 1 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 Hematopathy Diagnosis and Therapy Center, Kanghua Hospital, Dongguan, China 3 Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Southern Medical University, Guangzhou, China 5 Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China Correspondence to: Fanyi Meng, email: // Keywords : hypomenthylating agent, decitabine, refractory, relapse, AML Received : March 16 2015 Accepted : August 26, 2015 Published : September 10, 2015 Abstract In this study, we investigated the effect of pre-treatment with demethylating agent decitabine on susceptibility to chemotherapeutic drugs in HL60/ADR, Kasumi-1 and primary AML cells. Cytotoxic effect was increased by decitabine through activation of p53 and inhibition of c-Myc, Survivin and Bcl-2. We demonstrated in clinic that combination of decitabine and HAA consisting of harringtonine, aclarubicin and cytarabine was effective and safe to treat patients with refractory, relapsed or high-risk AML. Decitabine prior to HAA regimen improved the first induction complete response rate, and significantly prolonged overall survival and disease-free survival in these patients compared with HAA alone. These findings support clinic protocols based on decitabine prior to chemotherapy to overcome resistance and improve therapeutic efficacy in AML patients.