The new thrombopoietic agenda: impact on leukemias and MDS

The two generations of thrombopoietin (TPO) receptor (R) agonists have had utility in a number of hematologic conditions. However their use has often been surprisingly complex and drawbacks have been revealed in certain conditions more than in others. The first-generation megakaryocyte growth and development factor (MGDF) was discontinued due to the production of antibodies against it that cross-reacted with native TPO. Nonetheless it was tested in a wide variety of thrombocytopenic conditions and showed unequivocal efficacy in increasing the number of platelets in certain ones. As a result of lessons learned with MGDF, second-generation TPO-R agonists romiplostim and eltrombopag were initially tested and have been approved for the treatment of chronic immune thrombocytopenia (ITP), thrombocytopenia in hepatitis C, and recently aplastic anemia. These agents have had more mixed outcomes in diseases such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Results of several studies will be discussed.