Therapy-related acute leukaemia with mitoxantrone: four years on, what is the risk and can it be limited?

Mult Scler. 2015 Apr;21(5):642-5. doi: 10.1177/1352458514541508. Epub 2014 Jul 10.

Abstract

Therapy-related acute leukaemia (TRAL) is a significant concern, when considering treatment with mitoxantrone for multiple sclerosis (MS). We re-evaluated the literature, identifying all case reports and series of > 50 patients reporting TRAL cases in MS. TRAL was diagnosed in 0.73% of the 12,896 patients identified. Median onset was 22 months following treatment. We calculated a number needed to harm of 137.5 exposed patients, significantly higher than our 2008 analysis. We found that 82.8% of patients were exposed to > 60 mg/m(2) with a relative risk of 1.85 (p = 0.018) compared to < 60 mg/m(2), strongly suggesting a relationship to dose. MS treatment regimens which limit the mitoxantrone dose to < 60 mg/m(2) reduce the risk of TRAL.

Keywords: Adverse effects; disease-modifying therapies; dosage; leukemia; mitoxantrone; multiple sclerosis; relapsing-remitting multiple sclerosis; therapy-related acute leukemia.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Leukemia / chemically induced*
  • Mitoxantrone / adverse effects*
  • Mitoxantrone / therapeutic use
  • Multiple Sclerosis / complications*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / complications
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy

Substances

  • Antineoplastic Agents
  • Mitoxantrone