Abnormal Heart Rhythm in Patients with Leukemia Treated with Arsenic Trioxide. Ann Intern Med. 2000;133:S59. doi: 10.7326/0003-4819-133-11-200012050-00007
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Published: Ann Intern Med. 2000;133(11):S59.
Acute promyelocytic leukemia (APL) is a cancer of the blood. Arsenic trioxide is effective in treating cases of APL that have not responded to other therapies. Abnormal heart rhythms are common in patients with arsenic poisoning, so there is concern that dangerous side effects might occur when arsenic is used to treat APL. A previous report found that heart rhythm abnormalities occurred in only 8 of 47 patients with leukemia receiving arsenic; none of these heart rhythms was life-threatening. However, another report described a patient with APL who required a pacemaker after arsenic treatment.
The researchers noticed an abnormality in the electrocardiogram of the first APL patient they treated with arsenic. They therefore decided to monitor a series of patients to see how often these abnormalities occur.
The study included 8 patients with APL who received arsenic therapy at a teaching hospital in Japan.
The patients were given arsenic trioxide through an intravenous catheter (a small tube inserted into a vein) daily for a maximum of 60 days. Treatment was stopped earlier if the leukemia went into complete remission, which means that no signs of the cancer could be found in the blood. Patients who went into remission were given an additional 25 days of arsenic therapy 3 to 6 weeks after the initial treatment. During arsenic treatment, the researchers monitored patients with ambulatory electrocardiography, which records the electrical activity and rhythm of the heart continuously while patients go about their usual activities. Patients also had standard electrocardiography once per week. This test measures the heart's electrical activity over a short period while the patient is resting.
Of the 8 patients, 5 went into remission. An abnormality of the electrocardiogram (prolonged QT interval) was noted in 4 of the 8 patients before they started arsenic treatments. This abnormality occurred in all of the patients during the first round of arsenic treatment and in 3 of the 4 patients who received another course of treatment after remission. Four patients developed types of abnormal heart rhythm that required treatment with drugs.
The number of patients studied was quite small, and half of the patients had abnormal electrocardiograms before receiving the drug. Moreover, the researchers did not study a control group of patients with APL who did not receive arsenic; the report therefore does not definitely prove that arsenic caused the heart abnormalities.
This report suggests that arsenic trioxide therapy can trigger abnormal heart rhythms and that patients with APL should have their heart rhythms monitored carefully while they are receiving arsenic therapy.
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The summary below is from the full report titled “Prolongation of the QT Interval and Ventricular Tachycardia in Patients Treated with Arsenic Trioxide for Acute Promyelocytic Leukemia.” It is in the 5 December 2000 issue of Annals of Internal Medicine (volume 133, pages 881-885). The authors are K Ohnishi, H Yoshida, K Shigeno, S Nakamura, S Fujisawa, K Naito, K Shinjo, Y Fujita, H Matsui, A Takeshita, S Sugiyama, H Satoh, H Terada, and R Ohno.
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