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Aplastische Anämie

Aktuelles zu Diagnostik und Therapie

Aplastic anemia

Current state of diagnosis and treatment

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Zusammenfassung

Die aplastische Anämie (AA) ist eine sehr seltene, in vielen Fällen lebensbedrohliche Erkrankung der Hämatopoese. Sie ist durch eine Bi- oder Panzytopenie bei gleichzeitiger Aplasie oder Hypoplasie der Hämatopoese charakterisiert. Es gibt angeborene und erworbene Formen. In den letzten Jahren wurde deutlich, dass auch bei einem Teil der Erkrankungen im Erwachsenenalter genetische Faktoren eine Rolle spielen, v. a. Mutationen in den Genen des Telomerasekomplexes. Therapieoptionen sind die allogene Stammzelltransplantation und die immunsuppressive Therapie. Die Therapieentscheidung hängt vom Schwergrad der Erkrankung, dem Alter und der Komorbidität der Patienten sowie von der Verfügbarkeit eines Stammzellspenders ab. Bei jungen Patienten mit einem passenden HLA-identischen Spender liegt die Überlebenswahrscheinlichkeit inzwischen über 90 %, sofern Knochenmark als Stammzellquelle gewählt wird und die Konditionierung mit einem Antithymozytenglobulin(ATG)-haltigen Schema erfolgt. Die Ergebnisse der Transplantation von einem HLA-kompatiblen unverwandten Spender haben sich im letzten Jahrzehnt deutlich verbessert, sodass für sehr junge Patienten zunehmend dieses Verfahren in der Erstlinientherapie in Betracht gezogen wird. Der Goldstandard in der immunsuppressiven Therapie ist ATG in Kombination mit Cyclosporin A (CsA). ATG, ein polyvalentes Antikörperpräparat, entsteht durch Immunisierung von Tieren mit humanen Thymozyten. ATG aus Pferden führt zu einer besseren Ansprechrate und Überlebenswahrscheinlichkeit als Kaninchen-ATG. Neue Studien zeigen ein trilineäres Ansprechen auf den Thrombopoetinrezeptoragonisten Eltrombopag bei ATG/CsA-therapierefraktären Patienten. In klinischen Studien wird Eltrombopag aktuell zusammen mit einer Immunsuppression als Primärtherapie geprüft.

Abstract

Aplastic anemia (AAI) is a rare life-threatening disorder which is characterized by bi- or tricytopenia and hypoplastic or aplastic bone marrow. AA can present as an acquired or congenital disorder. In recent years it was noted that a subgroup of patients with seemingly acquired AA with onset in adulthood carry mutations which cause or at least predispose to bone marrow failure, e.g. mutations in the genes of the telomerase complex. Options for first-line treatment are allogeneic stem cell transplantation or immunosuppression. The decision depends on severity of the disease, age and comorbidity of the patient and availability of a matched stem cell donor. Probability of survival after HLA-identical sibling transplantation exceeds 90 % in young patients with bone marrow as the stem cell source and conditioning with an ATG-containing regimen. Results of matched unrelated donor transplantation have improved substantially over the last 10 years. Matched unrelated donor transplantation is increasingly considered as the first-line treatment for very young patients who are candidates for transplantation, but lack an HLA-identical sibling donor. The gold standard for immunosuppression is the combination of antithymocyte globulin (ATG) and cyclosporine A (CsA). ATG, a polyvalent antibody preparation, is obtained from animals after immunization with human thymocytes. Response rate and overall survival after horse ATG treatment are significantly higher compared to rabbit ATG. Recent trials reported a surprisingly high rate of bi- and trilinear response to treatment with the thrombopoietin receptor agonist eltrombopag in patients refractory to immunosuppression. Ongoing trials now address the potential role of eltrombopag as an adjunct to immunosuppression in first-line treatment.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. H. Schrezenmeier und B. Höchsmann erhielten Unterstützung für Forschungsprojekte von Genzyme (jetzt Sanofi-Aventis), GlaxoSmithKline (jetzt Novartis) und Alexion. Ferner erhielten die Autoren Honorare für Vorträge und die Mitwirkung in wissenschaftlichen Beiräten von Alexion und Genzyme. Dieser Beitrag wurde unabhängig erstellt.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Institut für Transfusionsmedizin, Institut für Klinische Transfusionsmedizin und Immungenetik Ulm, DRK-Blutspendedienst Baden-Württemberg – Hessen und Universitätsklinikum Ulm, Helmholtzstr. 10, 89081, Ulm, Deutschland

    H. Schrezenmeier, S. Körper & B. Höchsmann

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  1. H. Schrezenmeier
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Schrezenmeier, H., Körper, S. & Höchsmann, B. Aplastische Anämie. Internist 56, 989–999 (2015). https://doi.org/10.1007/s00108-015-3662-7

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