Multiple sclerosisMonday, June 22, 2009, 17:30 - 19:00Incidence of acute leukaemia in multiple sclerosis patients treated with mitoxantrone: a multi-centre retrospective Italian study V. Martinelli, P. Bellantonio, R. Bergamaschi, A. Bertolotto, R. Capra, G. Cavalletti, E. Cocco, P. Gallo, C. Gasperini, A. Ghezzi, G. Mancardi, M. Ponzio, C. Pozzilli, M. Rodegher, G. Savettieri, L. Straffi, M. Trojano, G. Comi (Milan, Pozzilli, Pavia, Orbassano, Brescia, Cagliari, Padua, Rome, Gallarate, Genoa, Palermo, Bari, IT)
Objectives: Mitoxantrone (MTX) is an immunosuppressive drug worldwide approved for the treatment of patients with aggressive Multiple Sclerosis (MS). The use of MTX requires careful monitoring for potential severe adverse events. Previous studies reported an incidence of Acute Leukaemia (AL) from 0.07% to 0.25% in MS patients treated with MTX (dose < 140 mg/m2). We retrospectively collected data from a large cohort of Italian MS patients treated with at least one cycle of MTX, in order to detect the incidence of AL.
Material and methods: Up to now we have gathered a total of 2854 patients with relapsing-remitting (41%), primary progressive (8%) and secondary progressive (51%) MS, treated with MTX, since 1999, and observed for at least one year. Patients were identified by 36 Italian MS Centres. The following data were retrospectively collected: the total number of patients treated with MTX in each centre, the total cumulative dose (mg/m2), the duration of follow-up from the beginning of therapy to the last contact with the patient. Clinical features and cytogenetic analysis were recorded for every AL patient.
Results: So far we have observed 21 cases of AL, of whom 8 died. The cumulative incidence of AL was 7.4 per 1000; the incidence rate was 0.16 per 1000 person-month. Patients who presented AL received a greater number of MTX administrations (8.6 cycles vs 7.2 p<0.05) and a greater cumulative dose (82.4 vs 62.87 mg/m2 p<0.009) than patients who did not have AL. AL developed after an average period of 37 months from the beginning of MTX therapy and after a mean of 18 months from the end of treatment. Using as expositive factor the cumulative dose > 82.4 mg/m2 we observed an Incidence Rate Ratio of 2.74 (IC95% 1.06-7.35, p= 0.01).
Conclusions: The Incidence of AL in Italian MS patients treated with MTX is significantly higher than previously reported. The potential risks of AL, as well as the dose-related cardiotoxicity, should be carefully considered against the potential benefits of MTX treatment on every single MS patient. Moreover, all MS patients treated with MTX must undergo a prolonged and careful haematological follow up.
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