Therapy of acute promyelocytic leukemia: all-trans retinoic acid and beyond

Acute promyelocytic leukemia (APL) is the most potentially curable subtype of acute myeloid leukemia (AML). APL is highly sensitive to induction chemotherapy with anthracyclines. In addition, it now has been established that all-trans retinoic acid (ATRA), alone or in combination with chemotherapy for induction, improves the disease-free interval compared with chemotherapy alone. Large, prospective clinical studies have demonstrated complete remission rates ranging from 72% to 95% with ATRA therapy in patients with newly diagnosed APL. An important biological marker for monitoring residual disease is the promyelocytic retinoic acid receptor alpha (PML-RARalpha) fusion transcript. Its detection by the reverse transcription-polymerase chain reaction (RT-PCR) during remission appears to represent a strong predictor of clinical relapse. One limitation of ATRA therapy is the rapid development of retinoid resistance. Arsenic trioxide and alternative retinoids (9-cis retinoic acid and Am-80) currently are being investigated to determine whether they might have a role in circumventing retinoid resistance and further improving long-term outcome in patients with APL.