Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Department of Hematology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Hematology. 2023 Dec;28(1):2219930. doi: 10.1080/16078454.2023.2219930.
Anthracyclines and cytarabine have comprised standard induction therapy for acute myeloid leukemia (AML) for decades. Low overall survival of AML is due to non-remission or relapse after remission. Hypomethylating agent (HMA) decitabine combined with low-dose chemotherapy or other targeted agents has shown promising effect for AML in clinical trials, especially in (8;21) acute myeloid leukemia. We previously investigated histone deacetylase inhibitor (HDACi) chidamide could regulate Wnt/β-catenin signaling pathway in leukemia cell lines.
Adult patients with or relapsed/refractory AML who were treated with chidamide and decitabine in combination with chemotherapy (chidamide group, = 23) or only decitabine combination with chemotherapy (decitabine group, = 17) were analyzed.
Chidamide group represented higher complete response rate (82.6% and 52.9%, 0.0430, decitabine group), progression-free survival and overall survival rates (= 0.0088 and = 0.0139, respectively), especially for patients with AML. Hematological toxicity and infections were the most common adverse events (AEs) in both groups, and they were manageable by supportive treatments.
This HDACi- and HMA-based protocol is an effective and tolerable therapy for patients with AML. The comprehensive mechanism and effects of chidamide in combination with decitabine are worth to be further explored in AML.
阿霉素和阿糖胞苷已构成急性髓细胞白血病（AML）数十年的标准诱导治疗。AML 的总生存率低是由于缓解后未缓解或复发。低剂量化疗或其他靶向药物联合低甲基化剂（HMA）地西他滨已在临床试验中显示出对 AML 的有希望的效果，尤其是在（8；21）急性髓细胞白血病中。我们之前研究了组蛋白去乙酰化酶抑制剂（HDACi）西达本胺可调节白血病细胞系中的 Wnt/β-catenin 信号通路。
分析了接受西达本胺联合地西他滨联合化疗（西达本胺组，n=23）或仅接受地西他滨联合化疗（地西他胺组，n=17）治疗的复发/难治性 AML 成人患者。
西达本胺组完全缓解率（82.6%和 52.9%，0.0430，地西他胺组）、无进展生存期和总生存期率（=0.0088 和 =0.0139，分别）更高，尤其是对于 AML 患者。血液学毒性和感染是两组中最常见的不良事件（AE），支持性治疗可控制这些 AE。
这种基于 HDACi 和 HMA 的方案是 AML 患者有效且耐受良好的治疗方法。西达本胺联合地西他滨的综合机制和效果值得在 AML 中进一步探索。
