SEVERE CARDIAC FAILURE IN A PATIENT WITH MULTIPLE SCLEROSIS FOLLOWING LOW-DOSE MITOXANTRONE TREATMENT

Abstract

The synthetic antineoplastic anthracenedione mitoxantrone (MiTX) is well established as second-line treatment for worsening relapsing-remitting (RR) and secondary chronic progressive (SP) multiple sclerosis (MS).1 MiTX has a dose-related cardiotoxic potential which limits the cumulative lifetime dose in MS to 140 mg/m2. Up to a cumulative dose of 100 mg/m2, MiTX treatment is considered relatively safe.1,2 The risk of MiTX-induced congestive heart failure increases with the cumulative dose, previous treatment with anthracyclines, preexisting cardiovascular disease, and age. The development of acute severe heart failure shortly after initiation of MiTX treatment in MS has not been reported so far. Recently, the individual susceptibility to MiTX-induced side effects has been linked to naturally occurring genetic variations in ATP binding cassette (ABC) drug transporters.3 ### Case presentation. The diagnosis of RRMS was established in an otherwise healthy 26-year-old woman in 2003. In November 2005 and February 2006, she received 2 doses of MiTX (12 mg/m2 body surface area per infusion) due to high disease activity without any immediate periprocedural complications. Before application of the first and second dose, physical examination, echocardiography, and electrocardiogram were normal. Two months after the second pulse, the patient rapidly developed a severe acute biventricular cardiac failure with a left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) of 10%, severe pulmonary edema, aspiration pneumonia, and hepatic and renal failure. After stabilization by artificial ventilation, catecholamine substitution, and hemofiltration, cardiac function subsequently improved, with LVEF …