Frontline Management of Acute Myeloid Leukaemia Eligible for Intensive Chemotherapy

The phrase ‘Panta Rhei-everything flows’ by the Greek philosopher Heraclitus, a purported reference to a constantly changing flowing river, or more philosophically, ‘continual transformation’, can be aptly extended to describe the evolution of treatment strategies for many human diseases. In disappointing contrast, the drug treatment for patients with non-promyelocytic, acute myeloid leukaemia (AML) has remained essentially unchanged for over 50 years, with improved outcomes over this period, largely, a consequence of incremental improvements in supportive care and the application of allogeneic stem cell transplantation. The anti-leukaemic effectiveness of single-agent daunorubicin (D) or cytarabine (Ara-C) was first recognised over half-a-century ago, and intensified leukaemic cell kill with these genotoxic drugs (DA) became the standard approach for treating newly diagnosed AML patients. At the time of writing, induction therapy combining these two pharmacological classes of drugs, followed by intensified consolidation or allogeneic stem cell transplantation, remains the only proven strategy for curing AML. Here, through a review of the development of different anti-leukaemic drug combinations, we evaluate the effectiveness of various intensive chemotherapy platforms and the evidence for using adjunctive or sequential therapy with newer, genotoxic or non-genotoxic agents.