Use of arsenic trioxide (As₂O₃) in the treatment of patients with acute promyelocytic leukemia: The M. D. Anderson experience

BACKGROUND. Approximately 20-30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) and an anthracycline develop recurrent disease. It has been reported that arsenic trioxide (As₂O₃) is effective in this setting. The authors report the experience of The M. D. Anderson Cancer Center with As₂O₃ in the treatment of patients with recurrent APL. METHODS. Twelve patients who developed recurrent APL after treatment with ATRA were included. Patients received intravenous As₂O₃ 0.15 mg/kg per day until they achieved a complete remission (CR) or up to a maximum of 60 days. Their median age was 44 years (range, 26-72 years), and the median duration of first remission was 52 weeks (range, 23-292 weeks). RESULTS. All 12 patients achieved a CR. The median time to achieve CR was 52 days (range, 27-75 days). Seven of 10 evaluable patients achieved a molecular remission (i.e., polymerase chain reaction [PCR] analysis was negative for the gene encoding fusion of the nuclear receptor for retinoic acid to the PML gene at the time of CR; 70% of patients; 95% confidence interval, 0.35-0.93), and all other patients had negative PCR results after they received postremission therapy. All patients received subsequent therapy: Four patients received As₂O₃ alone, six patients received As₂O₃ with other chemotherapeutic agents, and two patients received idarubicin plus ATRA without As₂O₃. Eight patients continued in CR after a median follow-up of 24 months (range, 9-45 months). Side effects were mild, except for two patients who developed Grade 2 and 3 peripheral neuropathy, respectively; one of those patients required discontinuation of therapy. CONCLUSIONS. As₂O₃ is effective and well tolerated therapy for patients with recurrent APL. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable.