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Prolongation of the QT Interval and Ventricular Tachycardia in Patients Treated with Arsenic Trioxide for Acute Promyelocytic Leukemia

Kazunori Ohnishi, MD; Hitoshi Yoshida, MD; Kazuyuki Shigeno, MD; Satoki Nakamura, MD; Shinya Fujisawa, MD; Kensuke Naito, MD; Kaori Shinjo, MD; Yota Fujita, MD; Hirotaka Matsui, MD; Akihiro Takeshita, MD; Shiho Sugiyama, MD; Hiroshi Satoh, MD; Hajime Terada, MD; and Ryuzo Ohno, MD
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Copyright ©2004 by the American College of Physicians

Ann Intern Med. 2000;133(11):881-885. doi:10.7326/0003-4819-133-11-200012050-00012
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Background: Recently, arsenic trioxide has increasingly been used for relapsed acute promyelocytic leukemia. However, it is known to have several adverse effects, including acute cardiac toxicities.

Objective: To determine cardiac toxicities resulting from arsenic trioxide therapy in patients with relapsed or refractory acute promyelocytic leukemia.

Design: Phase II clinical prospective cohort study.

Setting: A university hospital in Hamamatsu, Japan.

Patients: 8 patients with relapsed acute promyelocytic leukemia.

Intervention: Arsenic trioxide, 0.15 mg/kg of body weight, administered daily by 2-hour infusion for a maximum of 60 days.

Measurements: Continuous monitoring with ambulatory electrocardiography.

Results: Five patients (63%) achieved complete remission. During induction therapy with arsenic trioxide, prolonged QT intervals were observed in all patients. Ventricular premature contractions were noticed during 8 of 12 courses of therapy. Four patients developed nonsustained ventricular tachycardia and required treatment with antiarrhythmic agents.

Conclusions: Cardiac toxicity occurs during arsenic trioxide therapy in patients with acute promyelocytic leukemia. Such patients should be monitored for prolonged QT intervals and ventricular arrhythmia.


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Electrocardiographic tracing and QT intervals in patient 1 during arsenic trioxide therapy.

Patient 1 received arsenic trioxide until day 43. Seven successive ventricular premature contractions developed on day 25, and mexiletine HCl was administered from day 28 to 148. VT = ventricular tachycardia.

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