Eltrombopag For Secondary Poor Graft Function Post Allogeneic Hematopoietic Stem Cell Transplantation

Overview

To investigate the efficacy and safety for secondary poor graft function (PGF) post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary objective is the hematologic response rate. Secondary objectives include: (1) incidence and severity of adverse events; (2) overall survival (OS), and disease-free survival(DFS).

Poor graft function (PGF) remains a life-threatening complication that occurs in 5-27% of patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is associated with morbidity and mortality related to infections or hemorrhagic complications. PGF is defined below: (1) with two or three cytopenic lines (hemoglobin ≤70 g/L, neutrophil count ≤0.5×109/L, platelet count ≤20×109/L) with transfusion requirements; (2) with hypoplastic bone marrow and full donor chimerism; (3) without relapse or severe graft versus host diseases(GVHD) or active infectious diseases, or drug-related myelosuppression; (4) last at least for 14 conductive days. Primary PGF refers to those who did not achieve hematopoietic engraftment at day +28 post-transplant, while secondary PGF(sPGF)was defined as PGF after full engraftment.The underlying pathogenesis of PGF remains unclear. Therapeutic approaches for PGF include (1) growth factors, including granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO)- stimulating factors and thrombopoietin(TPO) mimetics; (2) second allo-HSCT; (3) infusion of additional mobilized cells from the original donor (modified DLI); (4) Cluster of differentiation 34（CD34）positive selected and T cell-depleted stem cell boost(SCB) without conditioning. and (5) mesenchymal stem cell(MSC) transfusion. However, second allo-HSCT and infusion of additional unmanipulated stem cells are associated with high rate of GVHD and treatment-related mortality (TRM). Up to now, there is no standard treatment recommended for PGF patients. Eltrombopag is a kind of thrombopoietin receptor (TPO-R) agonists which can act as a stimulator of bone marrow progenitor cells.It has been approved by FDA for the treatment of immune thrombocytopenic purpura (ITP) and by European Union for severe aplasia anemia (SAA). Furthermore, there are also increasing amount of clinical trials using Eltrombopag for the treatment of thrombocytopenia post HSCT and very severe aplasia anemia(VSAA) which already had promising results. Due to the similarity in symptoms of PGF and AA, we suggested that if eltrombopag could be beneficial in patients with sPGF post allo-HSCT. In this single-center open study,20 cases with sPGF post- transplant will be enrolled.The starting dose will be 25mg daily for 3 days to see if the drug is tolerable and then increasing to 50mg for another week. Maintenance dosage is 50mg or 75 mg per day dependent on patients' status and doctors' opinion.Patients may stop medicine when they achieve persistent complete response for 2 weeks.If patients only get partial response or no response after 8 weeks of therapy they may either stop eltrombopag or continue the drug considering doctor's advice. Once a patient suffer severe adverse events,patients should discontinue the drug immediately and get supporting measures.

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