The thrombopoietin receptor agonist eltrombopag (EPAG) has been shown to restore hematopoiesis in patients with severe aplastic anemia (SAA) refractory to immunosuppressive therapy and to significantly improve response rates when used in combination with immunosuppressive therapy in treatment-naıve patients. 1-3 Patients with bone marrow failure are frequently iron overloaded as a result of chronic red cell transfusions. Recent in vitro studies suggested that EPAG mobilizes intracellular iron via direct chelation. 4, 5

To investigate the clinical significance of this observation, we analyzed plasma iron and ferritin levels in patients enrolled in 2 prospective clinical trials that used EPAG monotherapy to treat refractory severe aplastic anemia (refSAA; NCT01891994) or moderate aplastic anemia (MAA; NCT01328587). In patients with refSAA, EPAG was administered over a period of 6 months at a fixed dose of 150 mg once per day. Patients were evaluated for response after 3 and 6 months of treatment at the National Institutes of Health Clinical Center. Some patients discontinued the study before reaching the primary end point at 6 months. Patients with MAA were treated in a dose-escalating fashion (150-300 mg once per day) until the primary response end point of 3 to 4 months. Responding patients on both protocols continued EPAG on an extension arm until they met criteria for a robust hematologic response, at which time the drug was discontinued. In a few patients, EPAG was later restarted because of declining blood cell counts. Iron studies were performed at baseline, at response evaluations, and at periodic follow-up visits (every 6 months while receiving EPAG and at least once per year after EPAG was discontinued in responding patients).