Treatment of Relapsed Acute Promyelocytic Leukemia: a Review of the Literature

Abstract

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), in the majority of cases, characterized by the translocation t(15;17) (q22;q21.1), which fuses the genes encoding promyelocytic leukemia protein (PML) and retinoic acid receptor alpha (RARA). Previously associated with an extremely poor prognosis, APL is now considered a highly curable disease, following the introduction of target-therapy agents all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) into frontline treatment regimens. This progression in treatment towards reduced intensity and low toxicity regimens has allowed for notably improved outcomes and was facilitated by the improved understanding of the cellular and molecular biology of the disease, as well as of the mechanisms of action of some of the non-chemotherapeutic agents used to treat it. However, relapse still occurs in 10-15% of APL patients, mostly within the high-risk disease subset, thus emerging as one of the main causes of treatment failure in APL. Although ATO has also been proven to be highly effective in this setting, the optimal treatment for patients with relapsed APL is yet to be defined, and newly discovered resistance to this agent should be considered while selecting the best treatment regimen for relapsed patients, as well as for future development of alternative agents and approaches.