title: Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone.
abstract: Mitoxantrone is an approved drug for patients with worsening relapsing-remitting, secondary progressive and progressive relapsing multiple sclerosis (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 ventriculographies performed one to three months apart. Cardiotoxicity during the course of the treatment was not observed. However, three patients 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 treatment, 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 progression of disability and clinical exacerbations, our observation of a delayed cardiotoxicity makes necessary a long-term follow-up of MS patients treated with this drug.
authors.affiliation: Service de Neurologie, Cliniques Universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium. sophie.goffette@nchm.ucl.ac.be
authors.forename: Sophie
authors.initials: S
authors.lastname: Goffette
authors.forename: Vincent
authors.initials: V
authors.lastname: van Pesch
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Vanoverschelde
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Morandini
authors.forename: Christian J M
authors.initials: CJ
authors.lastname: Sindic
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use / Q000633:toxicity*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D008942:Mitoxantrone