APL in Developing Countries: ATO-Based Approach

Abstract

It is well recognized that arsenic trioxide (ATO) is an effective agent for the treatment of acute promyelocytic leukemia (APL). Use of single agent ATO in the treatment of APL leads to remissions which are durable in the majority, although few cases of primary resistance have been reported. The drug has been used both as a single agent and in combination with other conventional drugs to treat APL. Use of ATO is the accepted standard of care in the management of relapsed APL, where it is often used effectively as a bridge to a stem cell transplant. Currently, the combination of all-trans retinoic acid (ATRA) and ATO is considered the standard of care for newly diagnosed low- and intermediate-risk APL. ATO probably has multiple mechanisms of action. Better understanding of its mechanisms of action/s and synergy with other agents will likely lead to a more rationale use of this agent or its derivatives, either alone or in combination. There is limited data on the kinetics of leukemia clearance and normal hematopoietic recovery after the administration of single agent ATO for the treatment of APL, but preliminary data suggests that it is likely to be different from conventional therapy. There have been a number of concerns of the potential short- and long-term toxicity of this agent. Most such concerns arise from the toxicity profile noted in people exposed to long-term arsenic in the environment. The overall toxicity profile has been favorable with the therapeutic doses and schedules of administration of ATO in the treatment of malignancies. In a resource-constrained environment, the use of a single agent ATO-based regimen is a realistic and acceptable option to treat almost all patients with APL. In the developed world, it has the potential in combination with other agents to improve the clinical outcome with reduction of dose intensity of chemotherapy and remains an option for patients who would not tolerate conventional therapy. This chapter will focus on the use of single agent ATO and ATO-based non-myelosuppressive regimens as a treatment for APL, especially in a developing country.