[Therapeutic potential of thrombopoietin].
Thrombocytopenia induced by disease and/or chemotherapy is one of the major complications in the treatment of patients with hemato-oncological malignancies. The discovery of Mpl ligand, a hematopoietic growth factor that stimulates megakaryopoiesis and thrombopoiesis lineage-specifically both in vitro and in preclinical models, is an important step in the development of new treatment concepts for patients with thrombocytopenia. Two recombinant forms of Mpl ligand, recombinant human thrombopoietin (rHuTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), are currently being tested in clinical trials. Development of these thrombopoietins has recently been constrained due to the observation of anti-thrombopoietin antibodies in some patients following thrombopoietin treatment. However, clinical trials performed so far provide significant insight into the therapeutic potential of these molecules. TPO/MGDF stimulates thrombopoiesis in cancer patients before chemotherapy and reduces the duration and sometimes the degree of thrombocytopenia following myelosuppressive chemotherapy. Despite marked thrombocytosis in some of these patients an increased risk for thromboembolic complications was not observed. Although administration of TPO/MGDF has provided some clinical benefit after autologous bone marrow transplantation, such effects have not been found in the settings of peripheral blood stem cell transplantation and aplasiogenic AML chemotherapy. The potential role of Mpl ligand in other indications such as thrombocytopenia in liver disease, plateletpheresis and stem cell expansion remains to be determined. Recent efforts in the development of thrombopoietins focus on the generation of molecules with maintained thrombopoietic activity which are not immunogenic.
Geissler
K
K
Klinische Abteilung für Hämatologie und Hämostaseologie, Allgemeines Krankenhaus-Innere Medizin I, Wien, Osterreich.
D001792:Blood Platelets / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008107:Liver Diseases / Q000628:therapy; D009369:Neoplasms / Q000628:therapy; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013234:Stem Cells / Q000187:drug effects; D013921:Thrombocytopenia / Q000139:chemically induced / Q000209:etiology* / Q000628:therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*
D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin