title: Therapy-related acute leukaemia with mitoxantrone: four years on, what is the risk and can it be limited?
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.
authors.affiliation: The Walton Centre for Neurology and Neurosurgery, UK rjbellis@doctors.org.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Ellis
authors.affiliation: Countess of Chester, Chester, UK.
authors.forename: Sean
authors.initials: S
authors.lastname: Brown
authors.affiliation: Townsville Hospital, Queensland, Australia.
authors.forename: Mike
authors.initials: M
authors.lastname: Boggild
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007938:Leukemia / Q000139:chemically induced*; D008942:Mitoxantrone / Q000009:adverse effects* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D008942:Mitoxantrone
keywords: Adverse effects; disease-modifying therapies; dosage; leukemia; mitoxantrone; multiple sclerosis; relapsing-remitting multiple sclerosis; therapy-related acute leukemia