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Myelodysplastische Syndrome

Myelodysplastic syndromes

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Zusammenfassung

Unter dem Oberbegriff der „myelodysplastischen Syndrome“ (MDS) werden vielfältige Erkrankungen der hämatopoetischen Stammzelle zusammengefasst. Sie alle zeichnen sich durch eine ineffiziente Hämatopoese sowie dysplastische Veränderungen im Knochenmark aus. Im peripheren Blut fällt zumeist eine Anämie auf, die in der Regel makrozytär ist und ggf. von Neutropenie und Thrombozytopenie begleitet ist. Klinisch resultieren daraus Schwäche, Leistungsminderung und Abgeschlagenheit (Anämie), Blutungsneigung (Thrombozytopenie) sowie eine erhöhte Infektneigung (Neutropenie). Etwa ein Viertel aller Patienten mit MDS entwickelt im Laufe der Erkrankung eine akute myeloische Leukämie (AML), die durch eine Zunahme der Blastenzahl auf > 20 % im Knochenmark definiert ist. Eine Risikoeinteilung der Patienten in Bezug auf das Gesamtüberleben und die Transformation zur AML basiert auf dem International Prognostic Scoring System (IPSS) sowie auf dem neu formulierten IPSS-R. Dank neuer Sequenzierungsmethoden konnten viele rekurrente Mutationen bei MDS-Patienten identifiziert werden, insbesondere in Genen des Splicing-Apparats sowie in epigenetisch wirksamen Genen (ASXL1, TET2). Die Therapie richtet sich nach dem Risikoprofil des Patienten. Für Hochrisikopatienten in gutem Allgemeinzustand und einem biologischen Alter von ≤ 70 Jahren ist die allogene Stammzelltransplantation eine kurative Option. Ansonsten erfolgt bei hohem Risiko eine Behandlung mit demethylierenden Substanzen wie Azacitidin. Patienten mit niedrigem Risiko werden vornehmlich supportiv behandelt. Eine Sonderstellung nimmt das MDS mit Deletion 5q ein, das mit Lenalidomid sehr erfolgreich behandelt werden kann. Da die Therapie noch nicht optimiert ist, sollten betroffene Patienten unbedingt in klinische Studien eingeschlossen werden.

Abstract

Myelodysplastic syndrome (MDS) encompasses a heterogeneous group of diseases originating in hematopoietic stem cells and is characterized by inefficient hematopoiesis and dysplastic changes in the bone marrow. In peripheral blood patients show anemia (mostly macrocytic), frequently accompanied by neutropenia and thrombocytopenia. Thus, clinically the patients suffer from fatigue (anemia), increased bleeding (thrombocytopenia) and infectious complications (neutropenia). Approximately one quarter of MDS patients develop acute myeloid leukemia (AML) in the course of the disease, which is characterized by a 20 % or more increase of blasts in the bone marrow. The estimated overall survival as well as the risk for AML transformation can be calculated with the international prognostic scoring system (IPSS) as well as the revised IPSS score (IPSS-R). Novel sequencing methods (e.g. next generation sequencing) allow the detection of recurrent gene mutations in MDS patients. Genes of the splicing machinery as well as genes involved in epigenetic regulation (e.g. ASXL1 and TET2) are most frequently mutated in MDS. Therapy is selected based on the patient risk profile (IPSS). Allogeneic stem cell transplantation is a curative approach for high risk patients (i.e. IPSS int-2 and higher) with a good performance status and a biological age below 70 years. Otherwise, high risk patients are treated with demethylating agents (e.g. decitabine and azacitidine). Low risk patients (IPSS low and int-1) mainly receive supportive therapy including iron chelation. An exceptional position is presented by MDS with an isolated 5q deletion as it can be treated with lenalidomide with good success. Enrolling patients in clinical trials is strongly recommended to improve the prospects of this disease.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. F. Thol gibt an, dass kein Interessenkonflikt besteht. M. Heuser: Forschungsunterstützung durch Boehringer-Ingelheim und Bayer. A. Ganser: Beratungsgremien von Celgene und Takeda.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    F. Thol, M. Heuser & A. Ganser

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  1. F. Thol
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Correspondence to F. Thol.

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Thol, F., Heuser, M. & Ganser, A. Myelodysplastische Syndrome. Internist 56, 364–373 (2015). https://doi.org/10.1007/s00108-014-3598-3

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