Torsade de Pointes during oral arsenic trioxide therapy for acute promyelocytic leukemia in a patient with heart failure


Dear Editor, Intravenous arsenic trioxide (As2O3) is highly effective for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia [1, 2], yet the high rate of significant corrected QT (QTc) prolongation and risk of ventricular arrhythmias mandates standard 12-lead and continuous electrocardiographic (ECG) monitoring during treatment [3, 4]. Earlier studies have shown that oral As2O3 has similar bioavailability but less cardiotoxicity, making it an attractive alternative to the intravenous drug [5, 6]. Nevertheless, data were mainly based on patients with structurally normal hearts, while its side-effect profile on those with underlying heart diseases remains undefined. Here, we present a patient with dilated cardiomyopathy who developed multiple arrhythmias during treatment with oral As2O3 therapy for acute promyelocytic leukemia. A 74-year-old man presented initially with oral mucosal bleeding. A full blood count showed pancytopenia (hemoglobin 9.5 g/dL, white cell count 1.0×10/L, and platelet count 9×10/L). There was coagulopathy with prolonged prothrombin time and activated partial thromboplastin time, and elevated D-dimer (>5,000 ng/mL, reference range <500 ng/mL). Bone marrow examination showed a hypercellular marrow that was replaced by abnormally hypergranular promyelocytes. Metaphase cytogenetics analysis of the bone marrow aspirate showed t(15;17) (q22;q12). Overall features were consistent with acute promyelocytic leukemia. The patient was referred to our center for further management. His medical history was significant for idiopathic cardiomyopathy and atrial fibrillation for 5 years, treated with ramipril 2.5 mg daily. Clinically, he was not fluidoverloaded or in congestive heart failure. Baseline electrocardiogram showed atrial fibrillation of 108 beats per minute with QTc of 393 ms. Transthoracic echocardiogram showed dilated left ventricle with left ventricular end-diastolic dimension of 5.8 cm, and left ventricular systolic function and ejection fraction impaired at 40 %. There was moderate mitral regurgitation secondary to left ventricular dilatation. Treatment with oral As2O3 and all-trans-retinoic acid was initiated. Standard 12-lead ECGs, 24-h Holter recordings, as well as plasma arsenic levels were monitored throughout the treatment period. During treatment with oral As2O3, progressive QTc prolongation was noted, which was strongly correlated with the pre-dose plasma arsenic level (r=0.91, p<0.01; Fig. 1). Serum potassium and magnesium were within normal limits during the whole treatment period. There were two separate episodes of ventricular tachyarrhythmias recorded during the treatment period. J. J. Hai :H.<F. Tse : C.<W. Siu Division of Cardiology, The University of Hong Kong, Hong Kong, China

DOI: 10.1007/s00277-014-2174-1

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@article{Hai2014TorsadeDP, title={Torsade de Pointes during oral arsenic trioxide therapy for acute promyelocytic leukemia in a patient with heart failure}, author={Jo - Jo Hai and Harinder S Gill and Hung-Fat Tse and Cyrus Rustam Kumana and Yok-Lam Kwong and Chung - Wah Siu}, journal={Annals of Hematology}, year={2014}, volume={94}, pages={501-503} }