Early Australian clinical studies with pegylated recombinant human megakaryocyte growth and development factor.

Abstract

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF, an Mpl ligand) is a truncated form of native thrombopoietin currently undergoing clinical development. A series of studies in Australia have examined the safety and biological activities of PEG-rHuMGDF. Administration of PEG-rHuMGDF causes a dose-dependent increase in platelet count but has no effect on white cell count or hematocrit. These platelets are morphologically and functionally normal. When administered following moderately myelosuppressive chemotherapy, PEG-rHuMGDF significantly enhances platelet recovery, although scheduling in relation to chemotherapy may be important in optimizing the full effects. PEG-rHuMGDF mobilizes progenitor cells of multiple hematopoietic lineages, and alters the kinetics of peripheral blood progenitor cell mobilization after chemotherapy and filgrastim. PEG-rHuMGDF is well tolerated and does not cause toxicity similar to that observed with other thrombopoietic cytokines. Numerous studies are underway to help determine the precise role of PEG-rHuMGDF in clinical practice.