MS Speaks

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

Richard Ellis
The Walton Centre for Neurology and Neurosurgery, UK
Sean Brown
Countess of Chester, Chester, UK

Mike Boggild
Townsville Hospital, Queensland, Australia
The Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley, Liverpool, L9 7LJ, UK rjbellis@doctors.org.uk

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/m2 with a relative risk of 1.85 (p = 0.018) compared to < 60mg/m2, strongly suggesting a relationship to dose. MS treatment regimens which limit the mitoxantrone dose to < 60mg/m2 reduce the risk of TRAL.