Pharmacologic treatment options in patients with thrombocytopenia.

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.
AuthorsG D Demetri
JournalSeminars in hematology (Semin Hematol) Vol. 37 Issue 2 Suppl 4 Pg. 11-8 (Apr 2000) ISSN: 0037-1963 [Print] UNITED STATES
PMID10831284 (Publication Type: Journal Article, Review)
Chemical References
  • Cytokines
  • Platelet-Derived Growth Factor
  • Recombinant Proteins
  • Thrombopoietin
  • Cytokines (physiology, therapeutic use)
  • Humans
  • Platelet-Derived Growth Factor (physiology, therapeutic use)
  • Recombinant Proteins (therapeutic use)
  • Thrombocytopenia (economics, therapy)
  • Thrombopoietin (physiology, therapeutic use)

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