Arsenic and APL: Review of Therapy for an Acute Leukemia

I was surprised to see an order for arsenic recently. What is this being used for? I thought arsenic went out with that old Cary Grant movie! —Name withheld on request

Arsenic is currently supplied in the United States as arsenic trioxide (Trisenox; also known as ATO). Arsenic trioxide is used in the treatment of acute promyelocytic leukemia (APL). Many induction and consolidation regimens for APL include arsenic trioxide in combination with all-trans retinoic acid (ATRA; tretinoin [Vesanoid]) and may include an anthracycline depending on if the patient’s APL is high-risk or low-risk. Depending on the initial APL treatment received, arsenic trioxide is an option in cases of relapsed APL and may be given with ATRA and an anthracycline.

Common adverse reactions to arsenic trioxide include leukocytosis, gastrointestinal side effects (eg, nausea, vomiting, diarrhea, abdominal pain), fatigue, edema, hyperglycemia, dyspnea and cough, rash, itching, headaches, and dizziness. Arsenic trioxide may also prolong the QTc interval and may cause AV block or torsades de pointes. Electrolytes should be monitored and corrected throughout treatment. In addition, the patient should be monitored via ECG prior to starting treatment and regularly during treatment with arsenic trioxide to reduce the risk of severe cardiac adverse events. 

Patients receiving induction therapy for APL, including those receiving arsenic trioxide, are also at risk of developing differentiation syndrome, which may include fever, dyspnea, weight gain, pulmonary infiltrates, pleural or pericardial effusions, and leukocytosis. If differentiation syndrome develops, patients should immediately be treated with high doses of corticosteroids.

Patients receiving arsenic trioxide should be counseled on the signs and symptoms of differentiation syndrome, and to report any symptoms experienced during the infusion. Arsenic trioxide is typically administered intravenously over 1 to 2 hours, but if patients experience acute vasomotor symptoms during treatment, the infusion can be extended to as long as 4 hours. Patients should also be educated to review any new medications with their health care team, to mitigate potential QTc prolongation. Other symptoms such as gastrointestinal side effects are generally mild and should be managed supportively.