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Maßgeschneiderte Therapie der chronischen myeloischen Leukämie

Tailored management of chronic myeloid leukemia

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Zusammenfassung

Ein optimales Management von Patienten mit chronischer myeloischer Leukämie unter Einsatz der besten Therapieoptionen erfordert eine konsequente zytogenetische und molekulare Verlaufskontrolle. Die Erstlinientherapie mit Tyrosinkinaseinhibitoren wird unter Beachtung des Nebenwirkungsspektrums von Begleiterkrankungen und den individuellen Therapiezielen beeinflusst. Klinische Prognosescores dienen dem Vergleich von Kohorten und der Stratifizierung in randomisierten Studien; ihre Bedeutung für die individuelle Therapiewahl ist nicht belegt. Wesentlich für therapeutische Entscheidungen ist das Erreichen zytogenetischer und molekularer Zielkriterien im Verlauf. Im Falle einer Therapieresistenz oder eines Rezidivs sollten mögliche Ursachen analysiert werden. Nach Ausschluss einer unzureichenden Compliance des Patienten werden eine Knochenmarkanalyse zur exakten hämatologischen Charakterisierung des Erkrankungsstadiums und zum Nachweis einer klonalen Evolution sowie eine BCR-ABL-Mutationsanalyse empfohlen. Die Wahl der Zweitlinientherapie richtet sich nach der Sensitivität eventuell nachgewiesener Mutationen und nach der klinischen Vorgeschichte des Patienten. Oberstes Therapieziel sollte die Verhinderung einer Progression sein; die Optionen für eine allogene Stammzelltransplantation sind frühzeitig zu prüfen. Dies gilt insbesondere für jüngere und fitte Patienten mit Hochrisikomerkmalen wie Multiresistenzmutationen.

Abstract

State of the art management of chronic myeloid leukemia (CML) patients with the selection of best available treatment options requires systematic cytogenetic and molecular monitoring. The choice of the first-line tyrosine kinase inhibitor depends on integration of comorbidities and individual treatment goals. Clinical prognostic scores should be used for cohort comparison and for stratification in randomized trials. Their relevance for individual treatment decisions has not yet been established. Essential for therapeutic decision-making is the achievement of predefined cytogenetic and molecular milestones in the course of the disease. In cases of treatment resistance or relapse the analysis of potential causes is required. After exclusion of compliance issues bone marrow analysis for the accurate characterization of the hematologic disease state and exclusion of clonal evolution is recommended. In parallel, BCR-ABL mutation analysis should be performed. The choice of second-line treatment depends on the predicted sensitivity of any BCR-ABL mutation detected and the clinical history of the patient. Most important is prevention of disease progression as treatment results in advanced disease are still not satisfying. Therefore, allogeneic stem cell transplantation should be considered early in resistant disease, when high-risk parameters (e.g. multiresistant mutations) have been detected.

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Interessenkonflikt

Der korrespondierende Autor weist für sich und seinen Koautor auf folgende Beziehungen hin: A. Hochhaus: Forschungsunterstützung und Honorare von Novartis, BMS, Ariad, Pfizer und MSD; P. La Rosée: Forschungsunterstützung und Honorare von Novartis, BMS, MSD und Pfizer.

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  1. Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07740, Jena, Deutschland

    A. Hochhaus & P. La Rosée

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  1. A. Hochhaus
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  2. P. La Rosée
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Correspondence to A. Hochhaus.

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Hochhaus, A., La Rosée, P. Maßgeschneiderte Therapie der chronischen myeloischen Leukämie. Internist 54, 155–163 (2013). https://doi.org/10.1007/s00108-012-3152-0

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