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Megakaryocyte Growth and Development Factor: A Review of Early Clinical Studies

Center for Development of Cancer Therapeutics, Parkville, Victoria, Australia

Correspondence: Dr. Russell L. Basser, Center for Development of Cancer Therapeutics, c/o P.O. Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Telephone: 61-3-9342-8792; Fax: 61-3-9347-7508; e-mail: basser{at}licre.ludwig.edu.au

Megakaryocyte growth and development factor (MGDF), a Mpl ligand, recently entered clinical trials worldwide and has been demonstrated to have potent biological activity. MGDF administration causes a dose-dependent increase in platelet count but no effect on white cell count or hematocrit. These platelets are morphologically and functionally normal. When administered following moderately myelosuppressive chemotherapy, MGDF significantly enhances platelet recovery, although scheduling in relation to chemotherapy may be important in optimizing the full effects. MGDF mobilizes progenitor cells of multiple hematopoietic lineages, and may enhance the effects of filgrastim on peripheral blood progenitor cell levels after chemotherapy. MGDF is well tolerated and does not cause toxicity similar to that observed with other thrombopoietic cytokines. Numerous studies are under way to help determine the precise role of MGDF in clinical practice.

Key Words. Thrombopoietin • Megakaryocyte growth and development factor • Platelets • Chemotherapy • Progenitor cell mobilization • Toxicity • Thrombocytopenia • Mpl ligand • c-mpl • Clinical • Human • Phase 1 • Aggregation • Platelet function • Safety

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