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

Abstract

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.

Definitive Setup of Clinical Scale Procedure for Ex Vivo Expansion of Cord Blood Hematopoietic Cells for Transplantation

“…This EPO-like domain is crucial for activation of c-MPL (myeloproliferative leukemia virus oncogene/CD110), the TPO receptor. The coupling to polyethyleneglycol (“PEGylation”) markedly increased the in vivo half-life of MGDF molecules without altering their ability to bind and activate c-MPL [reviewed in Abraham and Basser (1)]. Thus, PEG-MGDF, a clinical grade product, was used to obtain a positive effect on stem cell maintenance in course of ex vivo expansion, initially evidenced when TPO was associated with Flt-3L (23).…”

Thrombopoietin to replace megakaryocyte‐derived growth factor: impact on stem and progenitor cells during ex vivo expansion of CD34+ cells mobilized in peripheral blood

“…Thus, the biologic effects of TPO and MGDF are supposed to be comparable, if not identical. The “pegylation” (coupling to polyethylene glycol) markedly increased the half‐life of MGDF molecules without altering its ability to bind and activate c‐mpl (for MGDF biology, see review of Abraham and Basser 6 ). In this article, we are presenting the results demonstrating that PEG‐MGDF could be replaced by TPO during ex vivo expansion in our cultures, potentially enhancing the quality of expansion product.…”