Pediatric acute myeloid leukemia (AML) accounts for ∼20% of childhood leukemias and has been a clinical challenge due to its heterogeneity, high relapse rate and therapy-related toxicity. As compared to 90% overall survival in childhood acute lymphoblastic leukemia, event-free survival and overall survival remain suboptimal at 45% and 65%, respectively at three years and nearly half of children will relapse. Treatment protocols for pediatric AML have converged to a standard that includes four or five cycles of intensified myelosuppressive chemotherapy with cytarabine and anthracyclines followed by hematopoietic stem cell transplantation (HSCT) for a subgroup of patients. It is clear that the ceiling to further intensification of standard chemotherapy has been reached in AML, urgently necessitating novel therapeutic strategies. Recent developments in comprehensive mutation testing and integration of data from adult clinical trials led physicians try novel agents in pediatric AML patients especially in the relapse/refractory setting. In this context major treatment modalities and novel drugs in childhood AML include immunotherapy including drug-antibody conjugates and chimeric antigen receptor T-cell (CAR-T cell) therapy, epigenetic modifiers, tyrosine kinase inhibitors,and other novel agents. The addition of gemtuzumab ozogamicin and FLT3 inhibitors to some standard chemotherapy protocols has been becoming a standard of care in treatment of pediactric AML. Besides, major advances have also been achieved in acute promyelocytic leukemia (APL). The combination of ATO and ATRA without chemotherapy is now the standard chemotherapy for adults that are in the standard risk. Based on these findings; recent trials on pediatric APL patients aim to use ATRA plus ATO while minimizing the use of chemotherapy.

Recently, considerable progresses have been achieved in defining the molecular landscape of AML that lead scientists to discovery of novel drugs. There have been numereous ongoing studies on new therapeutic agents for AML, and some of them have already been included in the standard treatment protocols, but further studies on other new agents are needed to determine their efficacy in children.