title: Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone.
abstract: OBJECTIVE
  To evaluate the incidence and dose-dependency of mitoxantrone (MTX)-associated acute myelocytic leukemia (AML) in the network of Italian multiple sclerosis (MS) clinics.
  
  
  METHODS
  We performed a multicenter retrospective cohort study of patients treated with MTX in MS centers under the Italian national health care system between 1998 and 2008. Demographic, disease, treatment, and follow-up information were collected using hospital records.
  
  
  RESULTS
  Data were available for 3,220 patients (63% women) from 40 Italian centers. Follow-up (mean ± SD) was 49 ± 29 months (range 12-140 months). We observed 30 cases of AML (incidence 0.93% [95% confidence interval 0.60%-1.26%]). The mean cumulative dose was higher in patients with AML (78 vs 65 mg/m(2), p = 0.028). The median interval from the start of therapy to AML diagnosis was longer than expected at 33 months (range 13-84 months); 8 patients (27%) developed AML 4 years or more after the first MTX infusion. The rate of mortality associated with AML was 37%.
  
  
  CONCLUSIONS
  This higher than expected risk of AML and related mortality requires that treatment decisions must be made jointly between clinicians and patients who understand their prognosis, treatment options, and treatment-related risks. The now large exposed MS population must be monitored for hematologic abnormalities for at least 6 years from the end of therapy, to ensure the rapid actions needed for early diagnosis and treatment of AML.
authors.affiliation: Department of Neurology, INSPE, San Raffaele Scientific Institute, Milan, Italy. martinelli.vittorio@hsr.it
authors.forename: V
authors.initials: V
authors.lastname: Martinelli
authors.forename: E
authors.initials: E
authors.lastname: Cocco
authors.forename: R
authors.initials: R
authors.lastname: Capra
authors.forename: G
authors.initials: G
authors.lastname: Salemi
authors.forename: P
authors.initials: P
authors.lastname: Gallo
authors.forename: M
authors.initials: M
authors.lastname: Capobianco
authors.forename: I
authors.initials: I
authors.lastname: Pesci
authors.forename: A
authors.initials: A
authors.lastname: Ghezzi
authors.forename: C
authors.initials: C
authors.lastname: Pozzilli
authors.forename: A
authors.initials: A
authors.lastname: Lugaresi
authors.forename: P
authors.initials: P
authors.lastname: Bellantonio
authors.forename: M P
authors.initials: MP
authors.lastname: Amato
authors.forename: L M
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: M
authors.initials: M
authors.lastname: Trojano
authors.forename: G L
authors.initials: GL
authors.lastname: Mancardi
authors.forename: R
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: C
authors.initials: C
authors.lastname: Gasperini
authors.forename: M
authors.initials: M
authors.lastname: Rodegher
authors.forename: L
authors.initials: L
authors.lastname: Straffi
authors.forename: M
authors.initials: M
authors.lastname: Ponzio
authors.forename: G
authors.initials: G
authors.lastname: Comi
mesh_terms: D000368:Aged; D000700:Analgesics / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced*; D008297:Male; D008942:Mitoxantrone / Q000009:adverse effects*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D000700:Analgesics; D008942:Mitoxantrone