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Zusammenfassung: Es liegen nur wenige systematische Daten vor, die untersuchen, inwieweit in der Versorgung onkologischer Patienten in Deutschland eine Überbehandlung stattfindet. Überbehandlung wird in der Onkologie bewusst im Bereich der adjuvanten Therapie in Kauf genommen. Der Behandlungsvorteil einiger Patienten rechtfertigt hier die Therapie vieler Patienten. Aufgabe zukünftiger Studien ist es, diejenigen Patienten besser zu identifizieren, die von einer Therapie profitieren. Im Bereich der Behandlung mit nichtkurativem Ziel werden in Dritt-, Viert- oder Fünftlinien-Chemotherapien häufig wissenschaftlich nicht begründete Hoffnungen gelegt. Eine autonome Entscheidung seitens des Patienten setzt hier die Kenntnis palliativmedizinischer Behandlungsmöglichkeiten voraus.

BackgroundChronic myeloproliferative disorders (CMPD) originate from a pluripotent haematopoietic progenitor cell but show a marked degree of heterogeneity, especially between Philadelphia chromosome positive and negative disease entities. Abnormal megakaryopoiesis is a frequent finding in CMPD, often associated with thrombocythaemic cell counts. Recent experimental data have suggested that the c-Mpl thrombopoietin receptor, together with its ligand thrombopoietin, are not only the major physiological regulators of megakaryopoiesis and platelet production, but also play a crucial role in chronic myeloproliferation.MethodsA total of 18 peripheral blood mononuclear cell samples obtained from patients with CMPD (chronic myelocytic leukaemia (CML), n = 10; polycythaemia vera (PV), n = 6; and primary thrombocythaemia (PTH), n = 2) were analysed for c-mpl mRNA using the reverse transcriptase polymerase chain reaction (RT-PCR). In another 20 patients (CML, n = 10; chronic megakaryocytic granulocytic myelosis (CMGM), n = 3; PV, n = 3; PTH, n = 4), we compared the number of haematopoietic progenitors expressing c-Mpl, as characterised by coexpression with the CD34 antigen, in the bone marrow using double immunofluorescence staining.Resultsc-mpl mRNA was detected in all samples from patients with CML analysed, whereas only two of six PV and one of two PTH samples were positive (p ≤ 0.008; χ² test). Expression of the c-mpl receptor gene was absent in healthy subjects used as controls. Similarly, an increase of c-Mpl expressing CD34 positive haematopoietic cells was detected in seven of 10 bone marrow aspirates obtained from patients with CML. Increased numbers of c-Mpl positive CD34 positive cells were found in only one of four patients with PTH, whereas in PV and CMGM the numbers of c-Mpl positive CD34 positive cells did not exceed normal values, despite thrombocythaemic cell counts.ConclusionsThese data confirm recent findings showing an impaired expression of the c-mpl thrombopoietin receptor gene in Philadelphia chromosome negative CMPD when compared with patients with Philadelphia chromosome positive CML. The relevance of this observation to the functional and morphological characteristics of abnormal megakaryopoiesis remains unclear. Thrombocythaemic cell counts and a mature phenotype in mega-karyocytes occur frequently in Philadelphia chromosome negative CMPD but require an intact c-Mpl receptor under physiological conditions. Therefore, further studies are warranted to elucidate the mechanisms contributing to megakaryo-poiesis in CMPD disease entities with decreased c-mpl gene expression.