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Impairment of heart rate variability control during arsenic trioxide treatment for acute promyelocytic leukemia

Leukemia volume 18, pages 647–648 (2004)Cite this article

TO THE EDITOR

All-trans retinoic acid (ATRA), Am80 and arsenic trioxide (As2O3) have marked a great advance in the management of patients with acute promyelocytic leukemia (APL). Among them, arsenic trioxide (As2O3) has marked a great advance in the management of patients with APL.1 However, cardiac toxicities related to As2O3 have been reported in patients with relapsed/refractory APL.2 Electrocardiographic abnormalities, such as QRS complex broadening, prolonged QT intervals, ST-segment depression, T-wave flattening, arrhythmia and atrioventricular block, have been reported in acute arsenic poisoning.2,3 We previously reported that certain adverse cardiac effects are associated with the use of As2O3 treatment for APL.2 Prolonged QTc, ventricular premature contractions (VPCs) and ventricular tachycardia (VT) were observed during As2O3 treatment by a wireless monitoring and a 12-lead electrocardiography. However, the mechanism of these abnormalities has not been elucidated. Most of relapse/refractory APL patients receiving As2O3 have been heavily treated with chemotherapeutic agents including anthracyclines. Therefore, cardiac toxicity may become more pronounced under As2O3 treatment. However, there are not enough techniques to select patients at risk of life-threatening cardiac toxicity.

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References

  1. Tallman MS, Nabhan C, Feusner JH, Rowe JM . Acute promyelocytic leukemia: evolving therapeutic strategies. Blood 2002; 99: 759–767.

    Article  CAS  Google Scholar 

  2. Ohnishi K, Yoshida H, Shigeno K, Nakamura S, Fujisawa S, Naito 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 

  3. Soinet SL, Frankel SR, Douler D, Tallman MS, Kantarjian H, Calleja E et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 2001; 19: 3852–3861.

    Article  Google Scholar 

  4. Task force of the European society of cardiology the North American society of pacing electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 1995; 93: 1043–1065.

  5. Tjeerdsma G, Meinardi MT, van der Graaf WTA, van den Berg MP, Mulder NH, Grijns HJGM et al. Early detection of anthracycline induced cardiotoxicity in asymptmatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables. Heart 1999; 81: 419–423.

    Article  CAS  Google Scholar 

  6. Chiang C-E, Luk HN, Wang T-M, Ding PYA . Prolongation of cardiac repolarization by arsenic trioxide. Blood 2002; 100: 2249–2252.

    Article  CAS  Google Scholar 

  7. Klassen CD . Heavy metals and heavy metal antagonists. In: Hardman JG, Limbird LE (eds) Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th edn. New York: McGraw-Hill, 1996, 1652–1659.

    Google Scholar 

  8. Fonseca MI, Lunt GC, Aguilar JS . Inhibition of muscarinic cholinergic receptors by disulfide reducing agents and arsenicals. Biochem Pharmacol 1991; 41: 735–742.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Internal Medicine, Hamamatsu University School of Medicine, Nagoya, Japan

    A Takeshita, A Uehara, K Shinjo, K Naito, N Sahara, K Yamazaki, H Katoh, T Kamikawa, K Ohnishi & H Hayashi

  2. Laboratory Medicine, Hamamatsu University School of Medicine, Nagoya, Japan

    A Takeshita & M Maekawa

  3. Aichi Cancer Center, Nagoya, Japan

    R Ohno

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  1. A Takeshita
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  2. A Uehara
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  3. K Shinjo
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  11. H Hayashi
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Correspondence to A Takeshita.

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Takeshita, A., Uehara, A., Shinjo, K. et al. Impairment of heart rate variability control during arsenic trioxide treatment for acute promyelocytic leukemia. Leukemia 18, 647–648 (2004). https://doi.org/10.1038/sj.leu.2403248

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  • DOI: https://doi.org/10.1038/sj.leu.2403248

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