Thrombopoietic growth factors in the treatment of immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a relatively common blood disorder related to the production of anti-platelet antibodies. It is now clear that platelet production is also substantially impaired in most patients. After the cloning of TPO and analogs, there were reported therapeutic successes in a few refractory ITP patients, but neutralizing antibodies led to the withdrawal of first-generation thrombopoietic growth factor from development. Second-generation thrombopoietic growth factors are now available that stimulate c-mpl but share no homology with the native hormone. Second-generation thrombopoietic growth factors have shown responses in 50-80% of ITP patients with only modest toxicity, and thus they offer another therapeutic option. The first of these agents to enter clinical trials and to be approved by the FDA is romiplostim, a once weekly subcutaneous peptibody. Eltrombopag is the second FDA-approved thrombopoietic growth factor and has the advantage of oral formulation. Some concerns persist on the potential of these agents to cause increased thrombosis risk, rebound thrombocytopenia on drug withdrawal, reticulin fibrosis of the marrow, and induction of malignancy, but these have not emerged as major problems in clinical trials.