Clinical studies with megakaryocyte growth and development factor (Mpl-ligand)

The haemopoietic growth factor mpl-ligand (also known as thrombopoietin, and Megakaryocyte Growth and Development Factor [MGDF] is a recently cloned and characterized megakaryocyte-active factor. Administration of MGDF to humans was associated with a dose-related increase in the platelet count with maximum levels observed between days 12-18. Platelets had normal appearance and functioned normally in assays of platelet aggregation and ATP-release. There was no evidence of platelet activation as assessed by platelet surface markers. The earliest detectable effect of MGDF was an increase in early (reticulated) platelets by day 3-4. MGDF also hastened recovery from thrombocytopenia when given after myelosuppressive chemotherapy. MGDF caused mobilisation into the blood of progenitor cells of multiple haemopoietic lineages, and was synergistic with G-CSF in this action after chemotherapy. MGDF was well tolerated with no adverse effects directly attributable to its administration. Further clinical evaluation is on-going.