How I Treat: Secondary Acute Myeloid Leukemia

Secondary acute myeloid leukemia (sAML) has traditionally been used to designate any AML disease arising from an antecedent hematologic disorder or following prior cytotoxic or radiation therapy. We now know sAML comprises multiple disease entities with distinct clinical and biological features: AML-myelodysplastic related (AML-MR), myeloproliferative neoplasm-blast phase (MPN-BP), and AML post-cytotoxic therapy (AML-pCT). These entities largely represent adverse-risk phenotypes with the majority of patients experiencing suboptimal outcomes with standard therapeutic options. Given the aging general population and the increased lifespan of individuals receiving DNA damaging agents for other medical conditions, the incidence of these diseases is steadily rising and now comprise approximately 25-30% of all new AML diagnoses. Despite the plethora of novel agents approved for AML since 2017, many are either not applicable to sAML (i.e. lacking a targetable mutation), have limited efficacy, or have not been studied in these specific entities. Furthermore, these patients are under-represented in clinical trials, and novel therapeutic options are critically needed. Here we present multiple patient cases exemplifying the new nomenclature and classification of the diseases comprising sAML and highlighting their diverse presentations. We provide our therapeutic approach for each clinical scenario and discuss the challenges of treatment with the currently available armamentarium.