Treatment of refractory aplastic anemia with eltrombopag: Experience of a center

Background: Eltrombopag, a thrombopoietin receptor agonist, was approved in 2008 for the treatment of immune thrombocytopenic purpura. More recently, benefits demonstrated in the proliferation and maintenance of hematopoietic stem and progenitor cells (HSTC) led to its use and approval in the treatment of severe aplastic anemia (AA) refractory to immunossupressive therapy. Aims: In this report, we evaluated response to eltrombopag in patients with refractory AA and associated side effects. Methods: Retrospective analysis of six patients with a diagnosis of aplastic anemia and thrombocytopenia (platelet count ≤30.000/uL), refractory to imunossupressive therapy and ineligible for allotransplant, treated with eltrombopag. Patients characteristics, response, clinical evolution and adverse effects were evaluated. Results: Four patients were female and median age at diagnosis was 66 years (36-76). Previous treatments included horse antithymocyte globulin (1), cyclosporine (4), intravenous immunoglobulin (1), corticosteroids (4) and danazol (1). Treatment with eltrombopag was associated to cyclosporine in four patients; two cases had chronic renal failure and consequent contraindication to cyclosporine. The median duration of treatment with eltrombopag at the time of this analysis was 7 months (3-12). At 3 months, all patients had platelet counts >30.000/uL (median increase, 16.500/uL). Five patients improved hemoglobin levels (median increase, 2.2g/dL); 3 of them were previously dependent on red cell transfusions, and no longer needed transfusions. Four patients increased neutrophil counts (median increase, 1110/uL). All but one patient received a maximum dose of 150mg per day. Only one patient needed temporary discontinuation due to hepatic abnormalities, that were rapidly resolved. One other patient had mild elevation of liver enzyme levels. No other relevant side effects occurred. Summary/Conclusions: Treatment with eltrombopag was associated with hematologic response of one or more hematopoietic lineage, independence of blood transfusions and improved quality of life of patients with refractory severe AA. Except for infrequent and reversible hepatic abnormalities, tolerability was excellent. Thus, eltrombopag might be used in situations where other measures have failed in patients who have no indication for allogeneic stem cell transplant. A caution, however, should be taken on the risk for clonal evolution that should be carefully screened and surveilled.