Introduction
Aplastic anemia (AA) is a bone marrow failure disease, which is mainly characterized by pancytopenia after immune destruction of hematopoietic cells. It is widely admitted that the main cause of AA is the immunological attack of bone marrow hematopoietic cells by dysfunctional T lymphocytes [1]. In North America and Europe, the annual incidence of AA is 2-6 per million [2]; the rate is 2 to 3-fold higher in Asia [3]. For children with severe aplastic anemia (SAA) having a matched sibling donor, allogeneic bone marrow transplantation remains the standard frontline therapy, while other patients should receive frontline immunosuppression therapy (IST) with rabbit anti-thymocyte globulin (rATG) combined with cyclosporine (CSA) [4]. The quality of hematological response to IST is higher than reported by adult studies [4-9], with overall response (OR) rates of 71.2%-74% and complete response (CR) rates of 23%–60%. Overall survival (OS) rates are also high, at 73.6%–93%; however, the CR rate needs to be improved, and long-term complications such as relapse and clonal evolution result in long-term event-free survival (EFS) rates of only 56–64% [5-10].
Eltrombopag is a small molecule thrombopoietin-receptor agonist available for oral administration. It starts a signal cascade reaction through the interaction with the thrombopoietin receptor transmembrane domain, to promote the proliferation and differentiation of bone marrow progenitor cells and induce hematopoiesis. A previous study found that administration of thrombopoietin receptor agonists represented by eltrombopag improves the therapeutic efficacy in aplastic anemia. The combination of eltrombopag and IST has been approved by the United States Food and Drug Administration (FDA) for cases aged ≥2 years as front-line treatment for SAA. Although the application of eltrombopag for SAA treatment in adults is relatively mature[11-13], reports on eltrombopag use in pediatric SAA are still scarce, with conflicting findings[14-16]. Therefore, we conducted a historical control study to evaluate the efficacy and safety of eltrombopag combined with IST for SAA in children.