Thrombocytopenia that results from
chemotherapy has become an increasingly important issue in the treatment of
cancer and remains a difficult clinical problem. The identification of a safe and effective platelet
growth factor could significantly improve the management of severe
chemotherapy-induced
thrombocytopenia. Over the past decade, a number of hematopoietic
growth factors with thrombopoietic activity have been identified, including
stem-cell factor (
c-kit ligand),
interleukin (IL)-1,
IL-3,
IL-6, and
IL-11, as well as
thrombopoietin (TPO) and its derivatives. Only a few of these agents have shown acceptable tolerability and sufficient ability to stimulate thrombopoiesis to justify testing in randomized clinical trials. Currently,
IL-11 is the only
cytokine licensed in the United States for treatment of
chemotherapy-induced
thrombocytopenia. However, its thrombopoietic activity is modest and its use is often associated with unfavorable side effects. Identification of TPO, the
c-Mpl ligand, as the primary physiologic regulator of megakaryocyte and platelet development offers important promise for treatment of
thrombocytopenia. Preliminary clinical studies of recombinant human TPO (rhTPO), a full-length glycosylated molecule, indicate that it is safe and biologically active in reducing severe
chemotherapy-induced
thrombocytopenia. In addition to rhTPO, the future may see the development of novel genetically engineered, high-affinity
cytokine receptor agonists and
c-Mpl ligand mimetic
peptides.