R Ellis1, M Boggild. 1. Walton Centre for Neurology and Neurosurgery, Neurological Sciences, Liverpool, UK. md0u3194@liv.ac.uk
Abstract
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/m(2)), timing and outcome of TRAL. RESULTS: Case-series including 5472 patients were identified; mean dose of Mitoxantrone was 74.2 mg/m(2) (range:12-120 mg/m(2)). 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/m(2), with a relative risk of 1.44 (CI95%:1.18-1.70) when comparing total dose >60 mg/m(2) against <60 mg/m(2) strongly suggesting a relationship between risk of TRAL and total dose.
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/m(2)), timing and outcome of TRAL. RESULTS: Case-series including 5472 patients were identified; mean dose of Mitoxantrone was 74.2 mg/m(2) (range:12-120 mg/m(2)). 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/m(2), with a relative risk of 1.44 (CI95%:1.18-1.70) when comparing total dose >60 mg/m(2) against <60 mg/m(2) strongly suggesting a relationship between risk of TRAL and total dose.
Authors: C Meyer; N Ansorge; I Siglienti; S Salmen; A Stroet; H Nückel; U Dührsen; P R Ritter; W E Schmidt; R Gold; A Chan Journal: Nervenarzt Date: 2010-12 Impact factor: 1.214
Authors: Elliot M Frohman; Gary Cutter; Gina Remington; Hongjiang Gao; Howard Rossman; Bianca Weinstock-Guttman; Jacqueline E Durfee; Amy Conger; Ellen Carl; Katherine Treadaway; Eric Lindzen; Amber Salter; Teresa C Frohman; Anjali Shah; Angela Bates; Jennifer L Cox; Michael G Dwyer; Olaf Stüve; Benjamin M Greenberg; Michael K Racke; Robert Zivadinov Journal: Ther Adv Neurol Disord Date: 2010-01 Impact factor: 6.570