title: Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
abstract: BACKGROUND
  From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy.
  
  
  OBJECTIVE
  To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS).
  
  
  METHODS
  Eight hundred and two patients from 12 MS centres (308 relapsing-remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6-12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after.
  
  
  RESULTS
  The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea.
  
  
  CONCLUSIONS
  This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS.
authors.affiliation: CHU Pontchaillou, Service de Neurologie, Rennes, France.
authors.forename: E
authors.initials: E
authors.lastname: Le Page
authors.forename: E
authors.initials: E
authors.lastname: Leray
authors.forename: G
authors.initials: G
authors.lastname: Edan
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced; D005260:Female; D005602:France; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects*; D007938:Leukemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects*; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D008942:Mitoxantrone