Recombinant human thrombopoietin: clinical experience and in vivo biology

Thrombopoietin (TPO) has rapidly moved from the laboratory to the clinic in less than 2 years since its cloning. Two forms of recombinant TPO have been developed for clinical use. The full-length molecule (Genentech Inc, San Francisco, CA) is referred to as recombinant human thrombopoietin, and the truncated version of the molecule (Amgen, Thousand Oaks, CA) is referred to as pegylated recombinant human megakaryocyte growth and development factor. Both of these forms have been evaluated in phase I/II clinical trials. Administration of either of these agents elicits an increase in circulating platelet counts by several-fold in patients who have normal hematopoiesis before chemotherapy. The response in platelets is accompanied by a significant increase in bone marrow megakaryocytes, an increase in frequency and the number of bone marrow progenitor cells of multiple cell lineages, and a marked mobilization of progenitor cells into the peripheral blood. The results of early trials suggest that TPO attenuates thrombocytopenia and enhances platelet recovery after chemotherapy. Several clinical trials are investigating the potential of this cytokine to enhance platelet recovery after high-dose chemotherapy with or without progenitor cell support, bone marrow transplantation, and leukemia treatment, and for increasing the apheresis yield of platelets in normal donors and cancer patients. Based on the encouraging results of the initial clinical trials, TPO holds promise as a useful therapeutic agent in the prevention and treatment of thrombocytopenia in cancer patients and other disorders.