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Eltrombopag vs. Recombinant Human Thrombopoietin to Increase Platelet Level After Hematopoietic Stem Cell Transplantation: a Non-inferiority, Open-label, Randomized-controlled Study

Hematopoietic stem cell transplantation (HSCT) is an important method to treat malignant tumor of blood system, and promoting platelets after HSCT is one of the important factors to determine the success of transplantation.

Recently, the main effective method to treat thrombocytopenia after transplantation is to preventively transfuse platelets. However, this method can cause platelet transfusion related graft-versus-host disease(GVHD), increase the risk of reaction and infection associated with blood transfusion, easily produce platelet related and specific antibodies (HPA), which seriously affect the curative effect of platelet infusion and even render platelet transfusion invalid. Besides, study has shown that the effective rate of platelet transfusion is 30%-70%, and the application of platelets in clinic is limited because of the shortage of blood supply at present.

Recombinant human thrombopoietin (rhTPO) is a glycoprotein molecule modified by full-length glycosylation and is of a similar pharmacological effect with endogenous thrombopoietin (TPO). TPO is a specific cytokine of megakaryocyte, which can promote the proliferation and maturation of macronuclear progenitor cells by binding to the receptor c-mpl. In addition, the chinese State Food and Drug Administration (SFDA) approved rhTPO for the treatment of thrombocytopenia after tumor chemotherapy in 2006. The study shows that rhTPO can increase the mean value of platelet count in the low period of platelet, shorten the time of low platelet, and improve the peripheral blood platelet aggregation rate in the bone marrow depression period.

Eltrombopag is the first oral non-peptide receptor (TPO-R) agonist, which can induce the proliferation and maturation of macronuclear progenitor cells via the Janus kinase (JAK) /signal transducer and activator of transcription (STAT) pathway. In 2008, the U.S. FDA approved the use of eltrombopag for the treatment of chronic idiopathic thrombocytopenia, and it has been widely used in tumor patients with thrombocytopenia after chemotherapy. Tanaka et al. have proved that eltrombopag can improve the average elevation of the platelet count in the bone marrow depression period in patients with stem cell transplantation. Besides, within the 9 patients receiving transplantation, the complete response of patients with primary and secondary thrombocytopenia were 60% and 71% respectively.

In China, studies showed that rhTPO could promote the recovery of platelet count, effectively reduce the infusion of platelet, decrease the risk of transplanting hemorrhage in acute leukemia patients after allo-HSCT. However, it is not clear that the effect of eltrombopag on improving platelet count after the treatment of HSCT. In addition, the comparison of efficacy and safety of eltrombopag vs rhTPO on platelet recovery after HSCT in clinical trial is not investigated. Therefore, it is of great significance to explore the efficacy and safety of eltrombopag and rhTPO in improving the recovery of platelet count after HSCT, which will provide a better method to recover platelet after HSCT.

The purpose of this study is to compare the efficacy of Eltrombopag vs rhTPO in complete response in patients after HSCT in China. To be more precise, Eltrombopag is taken 50 mg po daily from day 1 until platelet is completely effectively recovered after HSCT, while rhTPO is given by subcutaneous injection 15000 u daily from day 1 until platelet is completely effectively recovered after HSCT.

The primary endpoint was cumulative numbers of platelet engraftment (platelet recovery to ≥20 X 109/L for seven consecutive days without transfusion) on day 60 after transplantation