A study of therapy-related acute leukaemia after mitoxantrone therapy for                 multiple sclerosis

Ghalie, Richard; Mauch, E.; Edan, Gilles; Hartung, Hans‐Peter; Gonsette, R; Eisenmann, Stephan; Page, Emmanuelle Le; Butine, Michael D.; Goodkin, Donald E.

doi:10.1191/1352458502ms836oa

Cited by 143 publications

(70 citation statements)

References 19 publications

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“…The authors found the t-AML rate was found to be relatively low (0.15%). 97 Meanwhile, in a post-marketing report for mitoxantrone-treated multiple sclerosis patients from 2003 99 Pascual et al prospectively studied the rate of AML in two Spanish cohorts, from Valencia (n=142) and from Catalonia (n=88), of mitoxantrone treated multiple sclerosis patients. The cummulative incidence and incidence density of AML for the Valencian cohort were 2.82 and 0.62% respectively; and 2.27 and 0.44% for the Catalonian cohort.…”

Section: The Association Between Multiple Sclerosis and Myeloid Leukemiamentioning

confidence: 99%

Acute myeloid leukemia developing in patients with autoimmune diseases

Ramadan

Fouad

Summa³

et al. 2011

Haematologica

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Section: The Association Between Multiple Sclerosis and Myeloid Leukemiamentioning

confidence: 99%

Acute myeloid leukemia developing in patients with autoimmune diseases

Ramadan

Fouad

Summa³

et al. 2011

Haematologica

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“…25 An early review estimated that the risk of TRAL in the MS population was 0.07% after a mean follow-up of 36 months in 1,378 patients. 26 These data were based on the MIMS study 2 (124 patients) and the aforementioned multicenter French 8 (802 patients) and single-center German 9 studies (452 patients). No TRAL was seen in the MIMS or German cohorts, but one case was seen in the French study.…”

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confidence: 99%

Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis [RETIRED]

et al. 2010

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Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a "black box" warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report.Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results:The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ϳ12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ϳ0.4%, and leukemia occurs in ϳ0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions:The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. Neurology ® 2010;74:1463-1470 GLOSSARY AAN ϭ American Academy of Neurology; CHF ϭ congestive heart failure; CML ϭ chronic myeloid leukemia; FDA ϭ Food and Drug Administration; LVEF ϭ left ventricular ejection fraction; MIMS ϭ Mitoxantrone in Multiple Sclerosis Group; MS ϭ multiple sclerosis; MX ϭ mitoxantrone hydrochloride; NNH ϭ number needed to harm; RRMS ϭ relapsing-remitting multiple sclerosis; SPMS ϭ secondary-progressive multiple sclerosis; TRAL ϭ therapy-related acute leukemia; TTA ϭ Therapeutics and Technology Assessment.

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“…Ghalie et al 7 evaluated the incidence of therapy related acute leukemia after MX reviewing the records of 1,378 MX recipients in three MS studies (mean cumulative dose of 60 mg/m 2 and mean follow-up of 36 months) and found only one case of acute promyelocytic leukaemia (APML) detected five years after initiating MX (mean incidence proportion 0.07%). Brassat et al 6 detected only one case of trAML (FAB M5) (in a cohort of 802 French patients with MS treated with MX (incidence ≅ 0.25%).…”

Section: Discussionmentioning

confidence: 99%

Acute myeloid leukaemia induced by mitoxantrone: case report

Arruda

Montú

Oliveira

et al. 2005

Arq. Neuro-Psiquiatr.

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-Mitoxantrone (MX) is an immunosupressant drug used in secondarily progressive multiple sclerosis (SPMS) and in relapsing-remitting multiple sclerosis (RRMS). It has a leukemogenesis potential induced by cytogenetic abnormalities, though with a low incidence. Promyelocitic leukaemia (type M3) and other forms of acute myeloblastic leukaemias (M4 and M5) have been described in a few MS patients who received MX during their treatment. We describe a white female patient, 47 year-old, with SPMS (EDSS = 4) with 14 years of disease. She received MX during her disease and developed acute promyelocytic leukaemia (M3), with severe thrombocytopenia 30 months later. She ultimately died due to intracerebral hemorrhage. Other cases of treatment related to AML are reviewed and discussed.KEY WORDS: multiple sclerosis, mitoxantrone, acute myeloblastic leukemia. Leucemia mielóide aguda induzida por mitoxantrone: relato de casoRESUMO -Mitoxantrone (MX) é uma agente imunossupressor utilizado nas formas progressivas secundárias de esclerose múltipla (EM) ou formas surto-remissão sem resposta com outras formas de tratamento (p.ex. beta-interferon, acetato de glatirâmer). Com o uso desta medicação, ocorre uma incidência maior, embora pequena, de desenvolvimento de leucemia mielóide aguda induzida por quimioterápicos. Descrevemos o caso de uma paciente com forma progressiva secundária de EM, submetida a uma dose única de MX de 15mg e que 30 meses após desenvolveu quadro fulminante de leucemia promieloblástica aguda (M3), com trombocitopenia grave. A paciente faleceu por hemorragia intracerebral maciça. É feita revisão de outros casos relatados na literatura e os possíveis mecanismos de desenvolvimento desta complicação grave secundária ao uso do MX. PALAVRAS-CHAVE: esclerose múltipla, mitoxantrone, leucemia mielóide aguda.Mitoxantrone (MX) is a DNA-topoisomerase II inhibitor widely used in cancer therapy. In addition, mitoxantrone induces immunodepletion. It is the first immunosuppressant approved for worsening relapsing and secondary progressive multiple sclerosis (MS) 1,2 . The incidence of acute myeloblastic leukemia (AML) in the population of MS patients treated with mitoxantrone is higher than the estimated incidence proportion of de novo AML in the global population 3 .We report a case of fatal AML in a woman with MS who developed AML after use of MX. This is the first case of AML in a series of 25 patients with MS treated with MX in our Service. CASEA 47-year-old woman had a diagnosis of definite MS picture for 14 years. During the first months of 2001 she entered the secondarily progressive phase with progressive right spastic hemiparesis, neurogenic bladder, and

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A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis

Cited by 143 publications

References 19 publications

Acute myeloid leukemia developing in patients with autoimmune diseases

Acute myeloid leukemia developing in patients with autoimmune diseases

Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis [RETIRED]

Acute myeloid leukaemia induced by mitoxantrone: case report

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