Advances in the treatment of relapsed acute promyelocytic leukemia

The presence of the characteristic fusion transcript gene, promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha), provided hematologists with a rationale for the use of all-trans retinoic acid (ATRA) for differentiation therapy for acute promyelocytic leukemia (APL). Multiple studies have established that combination of ATRA and chemotherapy in newly diagnosed patients has increased the cure rate to 70% from 35% in patients treated with chemotherapy alone. However, still about 30% of the patients relapse and are often resistant to ATRA retreatment. Consequently, a number of novel agents that include several differentiation agents and monoclonal antibodies have been studied to provide improved outcomes for patients with APL who have relapsed. In particular, arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. The unique mechanisms of action by which arsenic trioxide exerts its effects are complementary to those of ATRA, potentially allowing for combination therapies with additive or even synergistic results. Within this context autologous or allogeneic bone marrow transplantations are also considered in second or subsequent relapse, especially after arsenic trioxide-induced complete remission in relapsing patients. Furthermore, molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse of APL before clinical relapse, ultimately improving chances of prolonged remission.