title: Revision of the risk of secondary leukaemia after mitoxantrone in multiple sclerosis populations is required.
abstract: 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.
authors.affiliation: Department of Neurology, Hospital Universitario La Fe, Valencia, Spain. med004201saludalia.com
authors.forename: Ana M
authors.initials: AM
authors.lastname: Pascual
authors.forename: Neus
authors.initials: N
authors.lastname: Téllez
authors.forename: Isabel
authors.initials: I
authors.lastname: Boscá
authors.forename: Javier
authors.initials: J
authors.lastname: Mallada
authors.forename: Antonio
authors.initials: A
authors.lastname: Belenguer
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Abellán
authors.forename: Angel P
authors.initials: AP
authors.lastname: Sempere
authors.forename: Pascual
authors.initials: P
authors.lastname: Fernández
authors.forename: Ma José
authors.initials: MJ
authors.lastname: Magraner
authors.forename: Francisco
authors.initials: F
authors.lastname: Coret
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalbán
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Casanova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D019083:Mediterranean Region / Q000453:epidemiology; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000188:drug therapy; D011446:Prospective Studies; D011994:Recombinant Proteins; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D008942:Mitoxantrone; D008775:Methylprednisolone