Retrospective Study Of Eltrombopag Combined With Cyclosporine A And Granulocyte-colony Stimulating Factor Treating Patients With Severe Aplastic Anemia

BackgroundAplastic anemia(AA)is a bone marrow failure syndrome characterized by pancytopenia.Immune abnormality plays an important role in the pathogenesis of AA The current standard first-line therapy for AA includes hematopoietic stem cell transplantation(HSCT)and immunosuppressive therapy(IST)based on antithymocyte globulin(ATG)and cyclosporine A(CsA).Even though with considerable effect,HSCT and IST are not suitable for every AA patient due to individual factors.Recently,Eltrombopag,a non-peptide thrombopoietin(TPO)receptor agonist has shown promise in treatment of AA.Overall response rate(ORR)of eltrombopag combined with IST based on ATG and CsA treating severe aplastic anemia(SAA)was approximately 90%.However,for those SAA patients ineligible for ATG,effect of eltrombopag combined with CsA and granulocyte-colony stimulating factor(G-CSF)remains unclearObjectiveTo explore the effect and safety eltrombopag,combining with CsA and G-CSF,in treatment of S AA patientsMethodsWe retrospectively analyzed clinical statistics of 12 SAA patients treated with eltrombopag,CsA and G-CSF in our center.Patients received 75 mg eltrombopag orally and 300?g/d G-CSF via subcutaneous injection,maintaining ANC>0.5x109/L as soon as the diagnosis was confirmed.CsA was administered at a dosage of 3mg/kg/d by intravenous injection for one week and then 6mg/kg/d orally thereafter.The CsA concentration was maintained at>100 ng/ml in plasma.Effect at 3 months,6 months and 1 year and adverse event were assessed.ResultsTwelve SAA patients were included in this retrospective study.The median age was 51(19-69)years.At the last follow-up,with a median follow-up time of 380(60-872)days,hematological response was observed in 9(75%)patients,with 5(42%)patients of CR and 4(33%)of OR.The median time to meet criteria of OR,CR and PR were 28(7-168),47(30-161)and 28(13-168)days,respectively.The median time to achieve neutrophil,erythoid and platelet(PLT)response were 29(7-178),33(24-178)and 28(13-171)days,respectively.11 patients presented with red blood cell(RBC)and all with PLT transfusion dependence before treatment.Median transfusion times were 4(4-51,2.5 units each time on average)and 5(3-36,1 unit each time)for RBC and PLT,respectively.The estimated cumulative ORR at 3,6 and 12 months after treatment were nearly 60%,70%and 80%.Among 10 acute SAA patients,ORR and complete response rate(CRR)were 80%and 50%.Except for 1 patient who relapsed after discontinuing eltrombopag suffered from septic shock repeatedly,none of the rest patients experienced severe infection.Only 2 patients presented ostalgia.Gastrointestinal reaction was observed in 2 patients.Transaminase elevated slightly in 1 patient.ConclusionEltrombopag combined with CsA and G-CSF treating SAA could induce high hematologic response rate without causing severe adverse effect.