title: Memorial lecture. Megakaryocytic growth factors: is there a new approach for management of thrombocytopenia in patients with malignancies?
abstract: C-mpl ligand acts primarily as a lineage-specific hematopoietic growth factor by promoting proliferation of megakaryocyte precursors and their differentiation into megakaryocytes and platelets. In addition to the ability of c-mpl ligand to support megakaryocytic development from CD34+ precursor cells, several lines of evidence also point to a stimulatory effect on hematopoietic stem cells. When recombinant thrombopoietin or pegylated megakaryocyte growth and development factor is administered to normal animals or humans, there is a dose-dependent increase in the platelet count. When administered following chemotherapy in animal models or humans, c-mpl ligands reduce the duration and sometimes the degree of thrombocytopenia. The issue of whether clinically relevant thrombocytopenia can be ameliorated has so far been more difficult to resolve. Because severe thrombocytopenia is not commonly seen with standard chemotherapy regimens, clinical studies examining c-mpl ligands for their ability to ameliorate chemotherapy-induced thrombocytopenia will focus on treatment of acute leukemias and bone marrow transplantation. The potential utility of c-mpl ligands for treatment of myelodysplastic syndromes, aplastic anemias, or in HIV infection, will have to be evaluated in the future. Possibly the greatest potential of thrombopoietic growth factors in the near future may be in transfusion medicine, to collect and to store platelets from healthy donors or in autologous settings.
authors.affiliation: Department of Haematology, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany.
authors.forename: W K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
mesh_terms: D000741:Anemia, Aplastic / Q000150:complications / Q000188:drug therapy; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D016190:Carboplatin / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000097:blood / Q000150:complications; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008253:Macaca mulatta; D008533:Megakaryocytes / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D015337:Multicenter Studies as Topic; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D010215:Papio; D010976:Platelet Count / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D013926:Thrombopoietin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D016190:Carboplatin