Sudden death among patients with acute promyelocytic leukemia treated witharsenic trioxide

Arsenic trioxide has been shown to be effective in treating acute promyeloc ytic leukemia (APL), with minimal overall toxicity reported to date. A phas e I/II study was initiated in June 1998 using arsenic trioxide for relapsed APL to determine the maximum tolerated or minimal effective dose and to de termine the efficacy of treatment at that dose. Ten patients received 1 to 4 monthly cycles of treatment with 0.1 mg/kg per day intravenous arsenic tr ioxide, Six of 7 patients evaluable for response achieved cytogenetic or mo lecular complete remission. However, 3 patients died suddenly during the fi rst cycle of treatment. Autopsies obtained on 2 of these failed to identify a cause of sudden death, despite evidence of pulmonary hemorrhage in one, A third patient, for whom an autopsy was not performed, became asystolic an d died while on continuous cardiac telemetry. These observations suggest th at arsenic trioxide may be significantly or even fatally toxic at doses cur rently used and that caution is warranted in its use. (C) 2001 by The Ameri can Society of Hematology.