J Neurol (2005) 252 : 1217–1222 DOI 10.1007/s00415-005-0839-3 ORIGINAL COMMUNICATION Sophie Goffette Vincent van Pesch Jean Louis Vanoverschelde Emmanuel Morandini Christian J. M. Sindic Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone Introduction Mitoxantrone (MTX) is an anthracenedione derivative structurally similar to anthracycline that was initially used as an antineoplasic agent with activity against a wide range of tumours at a maximal dose of 160 mg/m 2 [1]. Several clinical trials [2–9] have confirmed its effi- cacy in reducing both attack and progression rates in patients with worsening relapsing-remitting and pro- gressive multiple sclerosis (MS). The acute cardiotoxic- ity during MTX treatment is well documented [10] and considered to be low below a cumulative maximal dose of 140 mg/m 2 [11].Delayed cardiotoxicity in MS patients previously treated by MTX have not yet been described. In a group of 52 MTX-treated patients with a cumulative dose of about 144 mg/m 2 , we observed three patients with severe heart failure occurring 24, 39 and 80 months after the last MTX infusion. Methods MTX was used in 52 patients (range of age: 23 to 50 years) from a co- hort of 820 MS patients (6 %) between December 1991 and April 2003. None had pre-existing known cardiovascular diseases or arterial hy- JON 1839 Received: 16 August 2004 Received in revised form: 14 January 2005 Accepted: 19 January 2005 Published online: 18 April 2005 S. Goffette, MD · V. van Pesch, MD, PhD · C. J. M. Sindic, MD, PhD Service de Neurologie Cliniques Universitaires Saint Luc Université catholique de Louvain Brussels, Belgium Dr. S. Goffette () Service de Neurologie Cliniques Universitaires Saint Luc, UCL 10 Avenue Hippocrate 1200 Brussels, Belgium Tel.: +32-2/764-1082 Fax: +32-2/764-3679 E-Mail: sophie.goffette @nchm.ucl.ac.be J. L. Vanoverschelde, MD, PhD Service de Cardiologie Cliniques universitaires Saint Luc Université catholique de Louvain Brussels, Belgium E. Morandini, MD Service de Cardiologie Centre Hospitalier de l’Ardenne Libramont, Belgium ■ Abstract Mitoxantrone is an approved drug for patients with worsening relapsing-remitting, secondary progressive and pro- gressive relapsing multiple sclero- sis (MS). From a cohort of 820 MS patients, 52 (6 %) were treated with this drug between December 1991 and April 2003. Mitoxantrone was administered at a dose of 12 mg/m 2 once a month for three months and then at three-month intervals to reach a total cumulative dose of 144 mg/m 2 . The left ventricular ejection fraction was checked by radionuclide ventriculography prior to treatment and every six months. Treatment was stopped if the ejection fraction was below 50 % in two consecutive ventricu- lographies performed one to three months apart. Cardiotoxicity dur- ing the course of the treatment was not observed. However, three pa- tients developed congestive heart failure 24, 39 and 80 months after the last dose of mitoxantrone. Other cardiac causes were excluded. Two of these patients had been treated previously with cyclophosphamide. All patients first recovered on medical treat- ment, but two worsened a few months later. One patient remained severely symptomatic in spite of optimal medical treatment. Although mitoxantrone is generally well tolerated and reduces progres- sion of disability and clinical exac- erbations, our observation of a delayed cardiotoxicity makes nec- essary a long-term follow-up of MS patients treated with this drug. ■ Key words multiple sclerosis · mitoxantrone · long term follow-up · late cardiotoxicity