Thrombopoietic growth factors and cytokines

Chemotherapy-induced thrombocytopenia is largely managed with platelet transfusions and reductions of chemotherapy doses. In the last decade, several thrombopoietic cytokines have been investigated without much success. Thrombopoietin (TPO), a key physiologic regulator of platelet production, is found to be the most potent thrombopoietic cytokine studied so far. Unfortunately, the clinical development of recombinant human thrombopietin has met challenges related to the biology of TPO with a delayed peak platelet response and the findings of neutralizing antibodies to the pegylated molecule. Recent clinical studies showed the importance of TPO schedule in relation to chemotherapy. Also, recombinant TPO facilitated collection of platelets in normal donors and patients for transfusions. The initial trials in leukemia or transplant settings did not impact the need for platelet transfusions. Future developments of TPO and mimetics will require carefully designed clinical trials with the consideration of unique biology of TPO and the time lag for a peak platelet response.