Cancer Treatment Today

Thrombopoietic factors have only recently been introduced in clinical practice. With the discovery of thrombopoietin (TPO) and the development of a variety of peptide and non-peptide TPO receptor agonists, clinically effective thrombopoietic growth factors have now entered the clinical armamentarium. Two thrombopoietic growth factors have been approved for the treatment of chronic immune thrombocytopenia (chronic ITP) and one thrombopoietic growth factor has been approved for the treatment of thrombocytopenia in patients with hepatitis C who are being treated with interferon.
Patients with bone-marrow failure related to intrinsic disease processes, such as aplastic anemia and myelodysplastic syndromes, or chemotherapy induced aplasai, like in this case, have elevated endogenous thrombopoietin levels together with low circulating platelet counts. The response of these patients to pharmacologic doses of thrombopoietin would be limited, therefore, by the reserve of responsive stem cells. However, similar to erythropoietin, which is effective in approximately 20% of anemic patients with myelodysplastic syndromes, thrombopoietin may be effective in some patients with these disorders.

A recent small study by Olnes et al in the New England Journal of Medicine found that eleven of 25 patients (44%) had a hematologic response in at least one lineage at 12 weeks, with minimal toxic effects. Nine patients no longer needed platelet transfusions (median increase in platelet count, 44,000 per cubic millimeter). Six patients had improved hemoglobin levels (median increase, 4.4 g per deciliter); 3 of them were previously dependent on red-cell transfusions and no longer needed transfusions. Nine patients had increased neutrophil counts (median increase, 1350 per cubic millimeter). Serial bone marrow biopsies showed normalization of trilineage hematopoiesis in patients who had a response, without increased fibrosis. Monitoring of immune function revealed no consistent changes.

Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol 2013; 98:10.
Kuter DJ. Milestones in understanding platelet production: a historical overview. Br J Haematol 2014; 165:248.
Townsley DM, Desmond R, Dunbar CE, Young NS.Pathophysiology and management of thrombocytopenia in bone marrow failure: possible clinical applications of TPO receptor agonists in aplastic anemia and myelodysplastic syndromes.Int J Hematol. 2013 Jul;98(1):48-55
Matthew J. Olnes, M.D., Ph.D., Phillip Scheinberg, M.D., Katherine R. Calvo, M.D., Ronan Desmond, M.D., Yong Tang, M.D., Ph.D., Bogdan Dumitriu, M.D., Ankur R. Parikh, M.D., Susan Soto, B.S.N., Angelique Biancotto, Ph.D., Xingmin Feng, M.D., Ph.D., Jay Lozier, M.D., Ph.D., Colin O. Wu, Ph.D., Neal S. Young, M.D., and Cynthia E. Dunbar, M.D .Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia
N Engl J Med 2012; 367:11-19July 5, 2012