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Two Cases of Acute Promyelocytic Leukemia Complicated by Torsade de Pointes during Arsenic Trioxide Therapy


We describe 2 patients with acute promyelocytic leukemia (APL) in whom torsade de pointes (TdP) developed during treatment with arsenic trioxide. Patient 1 was a 23-year-old woman with second-relapse APL. Ventricular premature beat bigeminy developed on day 27 of treatment, and episodes of TdP developed on day 28. Patient 2 was a 51-year-old woman with second-relapse APL who had cardiomyopathy due to prior anthracycline treatment. TdP developed on day 17 of treatment. Arsenic trioxide is known to cause electrocardiographic abnormalities, such as ventricular tachycardia and prolongation of QT interval. Patient 1 was given fluconazole as a concomitant drug. Patient 2 had cardiomyopathy and hypokalemia. Careful management is needed during arsenic trioxide therapy because this treatment prolongs the QT interval, possibly inducing episodes of TdP.

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  1. Shen ZX, Chen GQ, Ni JH, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL), II: clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997;89:3354–3360.

    PubMed  CAS  Google Scholar 

  2. Soignet SL, Maslak P, Wang ZG, et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998;339:1341–1348.

    Article  CAS  Google Scholar 

  3. Goldsmith S, From AH. Arsenic-induced atypical ventricular tachycardia. N Engl J Med. 1980;303:1096–1098.

    Article  CAS  Google Scholar 

  4. Little RE, Kay GN, Cavender JB, Epstein AE, Plumb VJ. Torsade de pointes and T-U wave alternans associated with arsenic poisoning. Pacing Clin Electrophysiol. 1990;13:164–170.

    Article  CAS  Google Scholar 

  5. St Petery J, Gross C, Victorica BE. Ventricular fibrillation caused by arsenic poisoning. Am J Dis Child. 1970;120:367–371.

    PubMed  CAS  Google Scholar 

  6. Weinberg SL. The electrocardiogram in acute arsenic poisoning. Am Heart J. 1960;60:971–975.

    Article  CAS  Google Scholar 

  7. Barbey JT, Pezzullo JC, Soignet SL. Effect of arsenic trioxide on QT interval in patients with advanced malignancies. J Clin Oncol. 2003;21:3609–3615.

    Article  CAS  Google Scholar 

  8. Unnikrishnan D, Dutcher JP, Varshneya N, et al. Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide. Blood. 2001;97:1514–1516.

    Article  CAS  Google Scholar 

  9. Westervelt P, Brown RA, Adkins DR, et al. Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide. Blood. 2001;98:266–271.

    Article  CAS  Google Scholar 

  10. Ohnishi K, Yoshida H, Shigeno K, et al. Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Ann Intern Med. 2000;133:881–885.

    Article  CAS  Google Scholar 

  11. Ohnishi K, Yoshida H, Shigeno K, et al. Arsenic trioxide therapy for relapsed or refractory Japanese patients with acute promyelocytic leukemia: need for careful electrocardiogram monitoring. Leukemia. 2002;16:617–622.

    Article  CAS  Google Scholar 

  12. Drolet B, Simard C, Roden DM. Unusual effects of a QT-prolonging drug, arsenic trioxide, on cardiac potassium currents. Circulation. 2004;109:26–29.

    Article  CAS  Google Scholar 

  13. Ficker E, Kuryshev YA, Dennis AT, et al. Mechanisms of arsenic-induced prolongation of cardiac repolarization. Mol Pharmacol. 2004;66:33–44.

    Article  CAS  Google Scholar 

  14. Yamazaki K, Terada H, Naito K, et al. Arrhythmogenic effects of arsenic trioxide in patients with acute promyelocytic leukemia and electrophysiological study in isolated guinea pig papillary muscles. J Mol Cell Cardiol. 2004;37:268.

    Google Scholar 

  15. Naito K, Kobayashi M, Sahara N, et al. Prognosis of relapsed or refractory patients with acute promyelocytic leukemia treated with arsenic trioxide: comparison between the transplant cases and the non-transplant cases. In: Abstracts of the Japan Society for Hematopoietic Cell Transplantation Conference; December 16–17, 2004; Okayama, Japan. Abstract 159.

  16. Trisenox (arsenic trioxide) injection prescribing information. Seattle, WA: Cell Therapeutics; 2002.

    Google Scholar 

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Naito, K., Kobayashi, M., Sahara, N. et al. Two Cases of Acute Promyelocytic Leukemia Complicated by Torsade de Pointes during Arsenic Trioxide Therapy. Int J Hematol 83, 318–323 (2006).

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Key words

  • Acute promyelocytic leukemia
  • Arsenic trioxide therapy
  • Torsade de pointes