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When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

Arsenic has been known for centuries for its double-edged potential: a poison and at the same time a therapeutic agent. The name “arsenikon,” meaning “potent,” speaks itself for the pharmaceutical properties of this compound, questioned and analyzed for at least 2000 years. In the last decades, acute promyelocytic leukemia (APL) has evolved from a highly fatal to a curable disease, due to the use of all-trans-retinoic acid and, more recently, arsenic trioxide combinations. The success of these entirely chemo-free regimens increased the awareness of APL and reduced the prevalence of early deaths, which was an impending issue in this disease. Further improvements are expected with the next use of oral arsenic formulations, which will allow a complete outpatient approach, at least in the post-induction settings, further improving patients’ quality of life. The wide use of standardized approaches in APL will also help unravel long-standing open questions, including the pathogenesis, prevention, and treatment of the differentiation syndrome and of short-term organ toxicities. In the long term, the study of survivorship issues, such as fertility and organ-related and psychological damages, in the increasing number of survivors will help further improve their life after APL.