Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone

Neurology. 2011 Nov 22;77(21):1887-95. doi: 10.1212/WNL.0b013e318238ee00. Epub 2011 Nov 9.

Abstract

Objectives: 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.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Analgesics / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Italy / epidemiology
  • Leukemia, Myeloid, Acute / chemically induced*
  • Male
  • Mitoxantrone / adverse effects*
  • Multiple Sclerosis / drug therapy*
  • Retrospective Studies
  • Statistics, Nonparametric

Substances

  • Analgesics
  • Mitoxantrone