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.