title: Malignancies after mitoxantrone for multiple sclerosis: A retrospective cohort study.
abstract: OBJECTIVE
  To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis.
  
  
  METHODS
  This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence.
  
  
  RESULTS
  Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8-11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m(2) (interquartile range 50.8-102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval [CI] 1.05-2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20-6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39-24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs ≤75 mg/m(2)) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes.
  
  
  CONCLUSIONS
  While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable.
authors.affiliation: From the Department of Neurology (M.B., L.S., K.V.T.) and the Comprehensive Cancer Center Mainfranken (U.M.), University of Würzburg, Germany. m.buttmann@uni-wuerzburg.de.
authors.forename: Mathias
authors.initials: M
authors.lastname: Buttmann
authors.affiliation: From the Department of Neurology (M.B., L.S., K.V.T.) and the Comprehensive Cancer Center Mainfranken (U.M.), University of Würzburg, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Seuffert
authors.affiliation: From the Department of Neurology (M.B., L.S., K.V.T.) and the Comprehensive Cancer Center Mainfranken (U.M.), University of Würzburg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Mäder
authors.affiliation: From the Department of Neurology (M.B., L.S., K.V.T.) and the Comprehensive Cancer Center Mainfranken (U.M.), University of Würzburg, Germany.
authors.forename: Klaus V
authors.initials: KV
authors.lastname: Toyka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects* / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000453:epidemiology; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D008942:Mitoxantrone