Ji Yu-Ying, Zhang Wang-Gang, Chen Yin-Xia, Zhao Xin-Mei, He Ai-Li, Liu Jie, Wang Jian-Li, Wang Fang-Xia, Zhang Peng-Yu, Zhang Wen-Juan
Department of Hematology, The Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710004, Shanxi Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Feb;18(1):213-8.
The aim of this study was to explore the clinical efficiency and side effects of GHA-priming therapy on patients with acute monocytic leukemia, and to analyze its mechanism. 37 patients with refractory, relapse, hypocellular acute monocytic leukemia and elderly patients with AML-M(5) were treated with GHA-priming therapy (G-CSF, homoharringtonine and low dosage of cytarabine). Clinical efficiency, side effects, and therapy-relevant mortality were observed. By using U937 cell line as in vitro model, effect of G-CSF on cell cycle was determined by propidium iodide staining method. The inhibition rate, apoptosis rate of U937 cell line treated with various combination of G-CSF, homoharringtonine and cytarabine were detected by flow cytometry. The expression of MLAA34 on U937 before or after treating with chemotherapy was analyzed by immunohistochemical method. The results showed that in all the 37 patients, the total remission rate was 62.2% [complete remission rate was 45.95% (17/37) and partial remission rate was 16.2% (6/37)]. The incidence of granulocyte deficiency was 18.92% (2/37) with median time of 4 days. The severe infection occurred in 2 cases. No severe bleeding, no mild digestive effect occurred. Other non-hematological toxicities were low in vitro when incubated with G-CSF for 24 hours, the S-phase cells obviously increased. The inhibition rate, apoptosis rate and expression of MLAA34 of U937 cells treated by GHA significantly decreased as compared with cells treated with HA. It is concluded that the GHA priming therapy can be used to treat patients with refractory, relapse, senile and hypocellular acute monocytic leukemia with satisfied response rate and low hematological and non-hematological toxicities. G-CSF can enhance cytotoxicity of drugs such as Ara-C and HHT by promoting G(0) phase cells into the reproductive cycle. GHA and HA therapy can inhibit cell proliferation, induce apoptosis, and the former has a more significant function. GHA priming therapy can down regulate the expression of MLAA 34. MLAA-34 is a novel anti-apoptotic factor of acute monocytic leukemia.
本研究旨在探讨粒细胞集落刺激因子（G-CSF）联合高三尖杉酯碱（HHT）及小剂量阿糖胞苷（Ara-C）预激方案治疗急性单核细胞白血病（AML-M5）患者的临床疗效、不良反应并分析其作用机制。37例难治、复发、低增生急性单核细胞白血病患者及老年AML-M5患者采用G-CSF联合高三尖杉酯碱及小剂量阿糖胞苷预激方案进行治疗，观察其临床疗效、不良反应及治疗相关死亡率。以人组织细胞淋巴瘤细胞株U937为体外模型，采用碘化丙啶染色法检测G-CSF对细胞周期的影响；应用流式细胞术检测不同组合的G-CSF、高三尖杉酯碱及阿糖胞苷作用于U937细胞后的抑制率和凋亡率；采用免疫组化法分析化疗前后U937细胞中MLAA34的表达。结果显示，37例患者总缓解率为62.2%，其中完全缓解率为45.95%（17/37），部分缓解率为16.2%（6/37）。粒细胞缺乏发生率为18.92%（2/37），中位持续时间4天，发生严重感染2例，无严重出血及轻度消化系统不良反应发生，其他非血液学毒性较低。体外实验显示，G-CSF作用24小时后，S期细胞明显增加。G-CSF联合高三尖杉酯碱及阿糖胞苷作用于U937细胞后的抑制率、凋亡率及MLAA34表达均较高三尖杉酯碱联合阿糖胞苷作用组明显降低。结论：G-CSF联合高三尖杉酯碱及小剂量阿糖胞苷预激方案治疗难治、复发、老年及低增生急性单核细胞白血病疗效满意，血液学及非血液学毒性低。G-CSF可通过促使G0期细胞进入增殖周期，增强阿糖胞苷、高三尖杉酯碱等药物的细胞毒性。G-CSF联合高三尖杉酯碱及阿糖胞苷与高三尖杉酯碱联合阿糖胞苷均能抑制细胞增殖、诱导凋亡，前者作用更显著。G-CSF联合高三尖杉酯碱及阿糖胞苷预激方案可下调MLAA34表达，MLAA-34可能是急性单核细胞白血病新的抗凋亡因子。
