The priming induction regimen of HAG as a low dose chemotherapy strategy in AML clonal evolution.

Abstract

Chemotherapy employs chemical substances to interfere with the growth of cancer cells, and is a major treatment strategy in human cancer including acute myeloid leukemia (AML). Although they often effectively kill fast-dividing tumor cells, chemotherapeutic drugs also profoundly affect mutation spectrum of the tumor genome. Each chemotherapeutic drug has a working concentration within an appropriate range. Concentrations beyond this range will increase drug toxicity without adding clinical benefit, while concentrations below the range will result in an insufficient drug effect. The conventional strategy in oncology is to give a patient drugs at the maximum tolerated dose (MTD) in order to kill as many tumor cells as possible. However, this inevitably causes a high rate of toxicity to normal tissue, as well as resulting in new mutations and genome instability which can lead to drug resistance and relapse. The priming induction regimen of HAG (low dose of cytarabine (Ara-C) and Homoharringtonine (HHT) with granulocyte colony-stimulating factor (G-CSF) priming), has proven to be effective in subgroup of AML patients in small scale clinical studies. It is of great medical significance to explore whether low dose chemotherapy can reduce the side effect of chemotherapeutic drugs while maintaining the therapeutic benefits, and whether such alternative therapeutic strategy is advantageous compared to conventional intensive treatment regarding the development of drug resistance by affecting leukemic genome mutation load and clonal evolution in subgroup of AMLs.