Overview and Epidemiology of Pediatric AML

Acute myeloid leukemia (AML) is an acute malignancy characterized by clonal proliferation of immature myeloid cells, referred to as blasts. This clonal proliferation is driven by genetic and epigenetic changes that promote cellular growth and division, arrest cellular development in an immature state, as well as allow blasts to evade normal cell death pathways (Cassier et al., Br J Cancer 117(8):1089–1098, 2017). If left untreated, AML results in death in a matter of months or less (Oran and Weisdorf, Haematologica 97(12):1916–1924, 2012). Through decades of clinical trials and scientific investigation, modern medicine has significantly improved outcomes for pediatric AML patients to an approximate 70% overall survival rate in developed countries, often with the use of maximally intensive treatment (Rubnitz et al., Lancet Oncol 11(6):543–552, 2010; Aplenc et al., Haematologica 105(7):1879–1886, 2020). This correlates with approximately one in every three pediatric AML patients dying, and the price for cure among survivors includes a significant increase in long-term chronic health conditions (Bhatt et al., Leukemia 35(8):2258–2273, 2021). Further improvement is badly needed. Within AML, there is remarkable heterogeneity and a one-size-fits-all cure is unlikely to emerge. Buoyed by the example of AML subtypes that are now approaching cure rates in excess of 95%, ultimately the development of improved outcomes will rely on: (1) an improved understanding of AML biology, which in turn influences AML risk stratification, the ability to target AML genetic drivers, and our understanding of the contexts in which AML develops, (2) an improved ability to exploit vulnerabilities of AML blasts such as with newer therapeutics including cellular and immunotherapies, (3) through ongoing improvements in supportive care, and (4) improved access to care across ethnic groups and geographic locations. In this chapter, an overview of pediatric AML including relevant epidemiology will be presented. In subsequent chapters, the current state of the art for biology, diagnosis, treatment, and supportive care of pediatric AML in all its contexts will be comprehensively addressed.