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

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.