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Mitoxantron-assoziierte akute Leukämie bei Multipler Sklerose

Fallbericht und praktisches Vorgehen bei unklaren Zytopenien

Mitoxantrone-related acute leukemia by multiple sclerosis

Case report and practical approach by unclear cytopenia

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Zusammenfassung

Hintergrund

Aufgrund seiner hohen Effektivität in der Behandlung der schubförmig progressiven sowie sekundär progredienten Multiplen Sklerose (MS) hat Mitoxantron einen hohen Stellenwert in der Eskalationstherapie. Die therapieassoziierte akute Leukämie („therapy related acute leukemia“, TRAL) nach Mitoxantron-Applikation ist rezent in den Blickpunkt des Interesses gerückt.

Methodik

Der Fallbericht einer TRAL mit hämatologisch-onkologischer Differenzialdiagnostik wird aufgearbeitet und mögliche Risikofaktoren diskutiert. Die interdisziplinäre hämatologisch-onkologische sowie neurologische Entwicklung diagnostischer und therapeutischer Algorithmen bei unklarer Zytopenie unter Mitoxantron wird erörtert.

Ergebnisse

Wir beschreiben den Fall eines 34-jährigen MS-Patienten mit einer TRAL nach einer kumulativen Gesamtdosis von 45 mg/m2 Körperoberfläche Mitoxantron. Der Patient verstarb an einer Endokarditis. TRAL sind seltene aber schwerwiegende Komplikationen einer Mitoxantron-Therapie, allerdings mit einer breiten Streuung der berichteten Inzidenz. In der Literatur sind bislang keine sicheren Risikofaktoren und Abhängigkeiten von Vortherapien und von Therapieschemata identifiziert. Engmaschige Laborkontrollen sowie frühzeitige Knochenmarkpunktionen sind bei Verdacht auf eine TRAL essenziell, da die TRAL prinzipiell kurativ therapierbar ist.

Schlussfolgerung

Das Risiko einer TRAL ist bei der Indikationsstellung für eine Eskalationstherapie mit Mitoxantron zu berücksichtigen, wobei die exakte Inzidenz sowie Risikofaktoren (Dosierung, Therapieschema) noch unklar sind. Unter engmaschigem Monitoring sind die Risiken allerdings beherrschbar. Künftige Untersuchungen müssen auf die Identifizierung von Risikofaktoren von TRAL unter Mitoxantron-Therapie abzielen.

Summary

Background

Mitoxantrone is highly efficacious in the treatment of severe multiple sclerosis (MS). Mitoxantrone therapy-related acute leukemia (TRAL) has recently become the focus of interest.

Methods

A case report of fatal TRAL following mitoxantrone therapy is presented with a discussion on the differential diagnosis and risk factors. The interdisciplinary development of diagnostic and therapeutic algorithms is presented from a haematological and neurological point of view.

Results

We describe the case of a 34-year-old MS patient who developed TRAL following mitoxantrone therapy (cumulative dose 45 mg/m2 body surface). The patient died from endocarditis. TRAL is a rare but potentially fatal complication of mitoxantrone therapy with a wide variation of reported incidence. Thus far, no specific risk factors relating for example to preceding therapy and treatment regimens have been identified. Frequent laboratory controls and early bone marrow aspiration are mandatory for suspected TRAL as the condition is potentially curable.

Conclusions

TRAL needs to be considered in the risk-benefit assessment of mitoxantrone therapy, however, the exact incidence and risk factors (e.g. dosage, treatment regimen) are still unclear. The risks are controllable under close surveillance and early diagnosis is important for prognosis. Future investigations need to concentrate on identification of potential risk factors.

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Dr. Chan hat für Vortragstätigkeiten Honorare von Wyeth Pharma und Merck Serono erhalten. Er hat Forschungsunterstützung von Merck Serono erhalten.

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Authors and Affiliations

  1. Neurologische Klinik, St.-Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Gudrunstraße 56, 44791, Bochum, Deutschland

    C. Meyer, I. Siglienti, S. Salmen, A. Stroet, R. Gold &  A. Chan

  2. Medizinische Klinik I, St.-Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Bochum, Deutschland

    N. Ansorge, P.R. Ritter & W.E. Schmidt

  3. Westdeutsches Tumorzentrum, Klinik für Hämatologie, Universitätsklinikum Essen, Essen, Deutschland

    H. Nückel & U. Dührsen

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  1. C. Meyer
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  2. N. Ansorge
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  3. I. Siglienti
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  4. S. Salmen
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  5. A. Stroet
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  9. W.E. Schmidt
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  10. R. Gold
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  11. A. Chan
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Correspondence to A. Chan.

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Die beiden Erstautoren haben den gleichen Anteil zu diesem Beitrag beigetragen.

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Meyer, C., Ansorge, N., Siglienti, I. et al. Mitoxantron-assoziierte akute Leukämie bei Multipler Sklerose. Nervenarzt 81, 1483–1489 (2010). https://doi.org/10.1007/s00115-010-3041-5

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