In this study, the tolerability and safety of treatment with pulsed steroids and glatiramer acetate and the occurrence of clinical and radiological activity after natalizumab (NTZ) cessation in multiple sclerosis (MS) patients were assessed. MS patients with NTZ were discontinued after 2 years of treatment, or if adverse events or disease progressed during NTZ. They were offered as alternative treatment 1 g methylprednisolone per month during 3 months followed by daily 20 mcg glatiramer acetate and were prospectively studied. Adverse events, occurrence of immune reconstitution inflammatory syndrome, clinical exacerbations, and gadolinium-enhancing lesions in MRI performed at 3 and 6 months after NTZ cessation were recorded. EDSS change during follow-up was also recorded. A total of 18 MS patients entered the study and were followed up for a mean of 10 months (range 6-18 months). There were no significant adverse events. At month 3, no patient had clinical or radiological disease activity. At month 6, 16.6% of patients had had a relapse and 55.5% of patients showed gadolinium-enhancing lesions in the MRI. After 6 months, 33.3% of patients had a further relapse. There was no IRIS, severe relapses, or significant difference between EDSS at NTZ discontinuation and after follow-up. The alternative treatment with monthly prednisolone followed by GA prevents the development of IRIS, but not the return to previous inflammatory activity, which occurs between 5 and 6 months after NTZ withdrawal.
The objective in this paper is to compare the cumulative incidence and incidence density of therapy-related acute myeloid leukaemia in two cohorts of patients with multiple sclerosis treated with mitoxantrone, and with previously reported data in the literature. Six new cases of acute myeloid leukaemia were observed by prospectively following two Spanish series of 142 and 88 patients with worsening relapsing multiple sclerosis and secondary-progressive disease treated with mitoxantrone. A literature review shows 32 further cases of acute myeloid leukaemia reported, 65.6% of which are therapy-related acute promyelocytic leukaemia. Five cases in the cohorts fulfilled the diagnostic criteria for acute promyelocytic leukaemia, and one patient was diagnosed with pre-B-acute lymphoblastic leukaemia. Acute myeloid leukaemia latency after mitoxantrone discontinuation was 1 to 45 months. The accumulated incidence and incidence density was 2.82% and 0.62%, respectively, in the Valencian cohort, and 2.27% and 0.44% in the Catalonian cohort. In the only seven previously reported series, the accumulated incidence varied from 0.15% to 0.80%. The real incidence of acute myeloid leukaemia after mitoxantrone therapy in the multiple sclerosis population could be higher as evidenced by the growing number of cases reported. Haematological monitoring should continue for at least 5 years after the last dose of mitoxantrone. These data stress the necessity of re-evaluating this risk.
The presence of LS-OCMB in the first event suggestive of demyelination is related to an early increase in lesion load and brain atrophy. These data are in line with prospective studies showing the clinical prognostic value of LS-OCMB.
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