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Arsenic trioxide therapy for relapsed or refractory Japanese patients with acute promyelocytic leukemia: need for careful electrocardiogram monitoring

Leukemia volume 16, pages 617–622 (2002)Cite this article

Abstract

Recent studies have shown that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). We tested the efficacy and safety of As2O3 for the treatment of patients with APL who had relapsed from or become refractory to all-trans retinoic acid (ATRA) and conventional chemotherapy in a prospective study. As2O3 at a dose of 0.15 mg/kg was administered until the date of bone marrow remission to a maximum of 60 days. In patients who achieved complete remission (CR), one additional course of As2O3 was administered using the same dose for 25 days. Of 14 patients, 11 (78%) achieved CR. Six of 10 patients who achieved CR showed disappearance of PML-RARα transcript by RT-PCR assay. The duration of As2O3-induced CR ranged from 4 to 22 months (median, 8 months) at a median follow-up of 17 months. Adverse events included 13 electrocardiogram abnormalities (13 QTc prolongation, eight ventricular premature contraction, four nonsustained ventricular tachycardia and two paroxysmal supraventricular tachycardia), seven nausea and vomiting, four pruritus, three peripheral neuropathy, three fluid retention and one APL differentiation syndrome. Four patients received antiarrhythmic agents. Hyperleukocytosis developed in five patients and in three cytotoxic drugs were necessary. Other adverse events were relatively mild. As2O3 treatment is effective and relatively safe in relapsed or refectory patients with APL. Cardiac toxicities in patients with QTc prolongation should be carefully monitored.

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Acknowledgements

We express our sincere gratitude to Drs Masahito Ishibashi (St Marianna School of Medicine), Michio Ihara (Seirei Hamamatsu Hospital), Hiroshi Yamazaki (Kumamoto City Hospital), Tai-ichi Kawai (Fukui Medical University), Fumio Kawano (National Kumamoto Hospital), Kou Tanaka (Suzuka Kaisei General Hospital), Yuya Sugimoto (Hamamatsu Medical Center), Nobuhiko Emi (Nagoya University School of Medicine), Mitsuhiro Hashimoto (Nippon Medical School), Kazuteru Ohashi (Tokyo Metropolitan Komagome Hospital), Katsumichi Fujumaki (Kanagawa Cancer Center), Noriyuki Hirabayashi (Nagoya Second Red-Cross Hospital), Hirotsugu Kojima (Fujita Health University School of Medicine) and Masao Tomonaga (Nagasaki University School of Medicine) for treating the patients in this study. This study was partly supported by a Grant-in-aid for Cancer Research (No. 9–2) of the Ministry of Health, Labor and Welfare.

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Authors and Affiliations

  1. Department of Medicine III, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan

    K Ohnishi, H Yoshida, K Shigeno, S Nakamura, S Fujisawa, K Naito, K Shinjo, Y Fujita, H Matsui, N Sahara, A Takeshita, H Satoh & H Terada

  2. Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan

    R Ohno

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  1. K Ohnishi
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  2. H Yoshida
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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 16, 617–622 (2002). https://doi.org/10.1038/sj.leu.2402426

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