Comparative Study between Valproic Acid Combined with Conventional Chemotherapy Versus Conventional Chemotherapy Alone in Egyptian Acute Myeloid Leukemia Patients

Abstract

It has been postulated that inhibition of Histone Deacetylase (HDAC) can restore normal acetylation of histone proteins and transcription factors, and to be of benefit in the treatment of cancer. So, this study aimed at assessing the response to histone deacetylase inhibitor valproic acid combined with conventional chemotherapy versus conventional chemotherapy alone in Egyptian Acute Myeloid Leukemia (AML) patients. Thirty newly diagnosed AML patients were divided into 2 groups. Group 1 consisted of 15 AML patients received conventional chemotherapy while group 2 consisted of 15 AML patients received valproic acid 40 mg/kg for 7 days and conventional chemotherapy. Ten healthy persons of matched age and sex were considered group 3 (controls). Serum histone deacetylase activity, vascular endothelial growth factor, basic fibroblast growth factor, tumor necrosis factor α, glutathione S transferase and nuclear factor κB in nuclear extract before and after chemotherapy were measured in all patients and controls. Results revealed better clinical response with no side effects with valproic acid than conventional chemotherapy alone (p=0.021). This was associated with statistically significant decrease in histone deacetylase activity in patients receiving valproic acid compared to the other AML group (p=0.00019). There was significant negative correlation between age and HDAC activity at initial presentation in patients receiving valproic acid (p=0.039) while no significant correlation was detected with the other studied laboratory parameters. Our results revealed that valproic acid in the tested dose was safe and associated with better therapeutic response when used in combination with conventional chemotherapy.