Acute promyelocytic leukemia: recent advances in diagnosis and management

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) characterized by a specific genetic alteration, affecting the retinoic acid receptor-alpha (RARalpha), and leading to a blockage in the differentiation of the granulocytic cells. The accumulation of the promyelocytic blasts in the bone marrow produces intense peripheral blood cytopenias or, less commonly, hyperleucocytosis, both of which are frequently associated with a life-threatening consumptive coagulopathy. The body of available biological information on APL establishes this leukemia as a unique entity that has to be promptly recognized and clearly distinguished from all other acute leukemias, especially in light of its striking response to treatment with anthracyclines and differentiating agents such as all-trans retinoic acid (ATRA) or arsenic trioxide (ATO). Current state-of-the-art treatments, which include simultaneous administration of ATRA and anthracycline-based chemotherapy for induction and consolidation, as well as ATRA-based maintenance, have dramatically transformed APL into the most curable acute leukemia in adults, with approximately 80% of long-term survivors. Risk-adapted strategies to modulate treatment intensity may be an effective approach to minimizing therapy-related morbidity and mortality while maintaining the potential of cure. Nonetheless, a sizeable proportion of patients will relapse after the ATRA-based upfront therapy. Given the high anti-leukemic efficacy observed with ATO in patients who relapse, this agent is currently regarded as the best treatment option in this setting. In this article, we will review the current treatment strategies in the management of newly diagnosed and relapsed APL. We also highlight other aspects that can be crucial for the outcome of individual patients, including supportive care, recognition and treatment of life-threatening complications, management of ATRA- and ATO-associated adverse events, and the role of minimal residual disease (MRD) monitoring.