Efficiency of GHA priming therapy on patients with acute monocytic leukemia and its mechanism / 中国实验血液学杂志

ABSTRACT

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.