Long-term risk of leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis

Background: Mitoxantrone has been extensively used as a disease-modifying therapy for multiple sclerosis. However, estimates of the associated risk of therapy-related acute leukaemia and cardiomyopathy have been derived from short-term studies. This study aimed to ascertain the long-term risk of therapy-related acute leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis.

Methods: Between 2002 and 2010, 50 patients were treated with mitoxantrone at a single centre using a standard protocol (12 mg/m(2) body surface area monthly for 6 months as tolerated to a maximum of 72 mg/m(2) body surface area). Follow-up haematologic and echocardiographic data were collected in March 2011.

Results: Fifteen patients (30%) were excluded from analysis either because of lack of follow-up data, death due to non-cardiac and non-haematologic causes, or comorbid cardiovascular disease. The remaining 35 patients (70%) were followed for a median of 75 months (range: 9-103). The median cumulative mitoxantrone dose given was 72 mg/m(2) body surface area (range: 24-123). At the end of follow-up, no patients had developed therapy-related acute leukaemia. One patient suffered an asymptomatic drop in left ventricular ejection fraction from 55 to 47%.

Conclusion: This series of patients followed for up to 8.5 years suggests that the risk of either therapy-related acute leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis is low when patients are treated within standard protocol.