Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report

Abstract

Abstract In the past 6 years, we treated 129 patients who had acute promyelocytic leukemia (APL) with a new arsenic agent, oral tetra-arsenic tetra-sulfide (As4S4). Nineteen of the patients had newly diagnosed APL, 7 had first relapse, and 103 had hematologic complete remission (HCR). HCR was achieved in all patients with newly diagnosed APL and in all those with hematologic relapse. Of 16 patients with newly diagnosed disease and available cytogenetic and molecular analyses, 14 had cytogenetic and molecular complete remission (CR). Cytogenetic and molecular CR was also obtained in 5 of the 7 patients with hematologic relapse. In the HCR group, 35 of 44 patients positive for PML-RARα at baseline became negative. In the newly diagnosed group, estimated disease-free survival (DFS) rates for 1 and 3 years were 86.1% and 76.6%, respectively, with a median follow-up time of 13.5 months (range, 2-40 months). In the HCR group, DFS rates for 1 and 6 years were 96.7% and 87.4%, respectively, with a median follow-up of 23 months (range, 2-71 months). Treatment with As4S4 was well tolerated, with only moderate side effects, including asymptomatic prolongation of corrected QT interval, transient elevation in liver enzyme levels, rash, and mild gastrointestinal discomfort; neither myelosuppression nor appreciable long-term side effects occurred. Degeneration or apoptosis of APL promyelocytes was observed during As4S4therapy. Pharmacokinetic studies showed that the agent was absorbed rapidly. Most urinary arsenic excretion occurred within the first 24 hours. Both blood and urinary arsenic levels declined after discontinuation of As4S4. Our results show, for the first time, that As4S4 treatment alone is highly effective and safe in both remission induction and maintenance therapy in patients with APL, regardless of disease stage.