This Article Full Text (PDF) All Versions of this Article: 1352458508100967v1 15/4/505    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Ellis, R Articles by Boggild, M Search for Related Content PubMed PubMed Citation Articles by Ellis, R Articles by Boggild, M Social Bookmarking                         What's this?

Therapy-related acute leukaemia with Mitoxantrone: what is the risk and can we minimise it?

Walton Centre for Neurology and Neurosurgery, Neurological Sciences, Liverpool, UK md0u3194{at}liv.ac.uk

M Boggild

Walton Centre for Neurology and Neurosurgery, Neurological Sciences, Liverpool, UK

Background

Therapy-related acute leukaemia (TRAL) is a concern for neurologists and patients when considering treatment with Mitoxantrone for multiple sclerosis (MS). The timing of this complication, risk, mortality and relationship to exposure remain uncertain.

Methods

We searched literature for publications relating to Mitoxantrone in MS, reviewed publication references and handsearched abstract lists to identify case-series reporting follow-up and complications of treatment with Mitoxantrone. We combined this with our local database of 250 cases treated since 1997. We also identified all reported individual cases of TRAL and extracted data reporting exposure (dose or mg/m²), timing and outcome of TRAL.

Results

Case-series including 5472 patients were identified; mean dose of Mitoxantrone was 74.2 mg/m² (range:12–120 mg/m²). TRAL was diagnosed in 0.30% (1 in 333). In 34 TRAL cases, sufficient data was available to inform analysis of exposure. Onset was a median of 18.5 months following Mitoxantrone treatment (range:4–60). Acute Myelocytic Leukaemia and Acute Promyelocytic Leukaemia represented 46.4% each of the leukaemia subtypes. Six of 25 TRAL patients, where outcome was reported, died (24%). Over 80% of cases occurred in patients exposed to >60 mg/m², with a relative risk of 1.44 (CI95%:1.18–1.70) when comparing total dose >60 mg/m² against <60 mg/m² strongly suggesting a relationship between risk of TRAL and total dose.

Key Words: disease modifying therapies • mitoxantrone • multiple sclerosis

This version was published on April 1, 2009

Multiple Sclerosis, Vol. 15, No. 4, 505-508 (2009)
DOI: 10.1177/1352458508100967


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?