Zhao Huihui, Zhu Huayuan, Huang Jiayu, Zhu Yu, Hong Ming, Zhu Han, Zhang Jingjing, Li Shan, Yang Lijia, Lian Yun, Wang Shuai, Mao Jianping, Chen Yaoyu, Li Jianyong, Qian Sixuan
Department of Oncology, The Second Affiliated Hospital of Southeast University, Nanjing 210003, China; Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China; Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China.
Leuk Res. 2018 Mar;66:1-7. doi: 10.1016/j.leukres.2017.12.009. Epub 2018 Jan 2.
Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic.
The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous Vitamin C [IVC] plus DCAG [n = 39]) or DCAG (n = 34) treatment.
We found that low-dose Vitamin C and decitabine has a synergistic efficacy on proliferation, apoptosis, TET2 expression and activity, compared to drug-alone treatment in HL60 and NB4 cell lines in vitro. In clinic, feasibility and safety evaluations revealed that patients who received A-DCAG regimen have a higher complete remission (CR) rate than those who received the DCAG regimen (79.92% vs. 44.11%; P = 0.004) after one cycle of chemotherapy. The median overall survival (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, P = 0.039). Patients with adverse cytogenetics did benefit from CR. There was no clinically significant additional toxicity observed with the addition of IVC.
On the basis of these results, the addition of IVC at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG, in elderly patients with AML.
地西他滨广泛用于老年急性髓系白血病（AML）患者的治疗。低剂量维生素C也已被证明在细胞水平上可诱导DNA去甲基化。然而，低剂量维生素C在临床上是否与地西他滨具有协同作用尚不清楚。
研究了低剂量维生素C与地西他滨联合使用对HL60和NB4人白血病细胞的细胞增殖、细胞周期、凋亡以及TET2表达水平和活性的影响。此外，我们分析了73例接受A-DCAG（静脉注射维生素C [IVC]加DCAG [n = 39]）或DCAG（n = 34）治疗的老年AML患者的临床结局。
我们发现，在体外HL60和NB4细胞系中，与单独用药相比，低剂量维生素C和地西他滨在增殖、凋亡、TET2表达和活性方面具有协同疗效。在临床上，可行性和安全性评估显示，接受A-DCAG方案的患者在化疗一个周期后的完全缓解（CR）率高于接受DCAG方案的患者（79.92%对44.11%；P = 0.004）。A-DCAG组的中位总生存期（OS）优于DCAG组（15.3个月对9.3个月，P = 0.039）。细胞遗传学不良的患者确实从CR中获益。添加IVC未观察到临床上显著的额外毒性。
基于这些结果，在老年AML患者中，与DCAG相比，在DCAG方案中添加低剂量IVC似乎可提高CR率并延长OS。
