HEMONC: Fludarabine-induced bradycardia in a patient with refractory leukemia Fludarabine-induced bradycardia in a patient with refractory leukemia ================================================================================

Woei Chung-Lo, Ching-Yun Hsieh, Chang-Fang Chiu, Li-Yuan Bai

on 14/06/2010 10:06:00 To the Editor: A 22-year-old male diagnosed with acute myelogenous leukemia in November 2005 achieved complete remission after two courses of induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytosine arabinoside (200 mg/m2 in a 24-hour infusion for 7 days). He then received an additional two courses of cytosine arabinoside (3000 mg/m2) in a 3-hour continuous intravenous infusion twice daily for 3 days in April 2006 for intensification. Six months later, the leukemia relapsed and was refractory to re-induction chemotherapy (idarubicin 12 mg/m2 on days 1-3 and cytosine arabinoside 200 mg/m2 on days 1-7).With the exception of myelosuppression, no toxic events occurred during idarubicin and cytosine arabinoside treatment. Due to the refractoriness to re-induction chemotherapy, salvage chemotherapy with the FLAGI regimen (fludarabine 30 mg/m2 on days 1-5, cytosine arabinoside 2000 mg/m2 on days 1-5, and idarubicin 12 mg/m2 on days 7-8) was prescribed. Before chemotherapy, his vital signs were stable, with a blood pressure of 111/65 mm Hg, a respiratory rate of 19/min, a heart rate of 97/min, and a body temperature of 36.6ºC. An electrocardiogram (ECG) showed a normal sinus rhythm (Figure 1a). Premedication included dexamethasone, granisetron, and metoclopramide, which were prescribed in previous chemotherapy. Thirty minutes after the fludarabine infusion had been started, he developed sudden-onset general weakness, which lessened 5 minutes later. At that time, persistent bradycardia (48 beats per minute) was noted; vital signs were otherwise normal (blood pressure, 120/70 mm Hg; respiratory rate, 20/min; and body temperature, 36.1ºC). ECG revealed sinus bradycardia but no atrioventricular block, ST segment elevation or depression, or T wave inversion (Figure 1b). The patient did not have chest tightness or pain, dizziness, cold sweats, palpitations, dyspnea, or fever with chills. Investigations showed serum potassium 4.9 mmol/L (normal, 3.5-4.5 mmol/L), creatinine 1.0 gm/dL (normal, 0.5-1.3 g/dL), CPK 19 IU/L (normal, 38-174 IU/L), creatine kinase MB fraction 2.7 U/L (normal, 3-10 U/L), and troponin I < 0.04 ng/ml (normal,