An Optimum Proposal Of High-dose Dexamethasone As An Initial Therapy In Immune Primary Thrombocytopenia And Exploring Of Double Targets Concerted Intervention

BackgroundPrimary immune thrombocytopenia (ITP) is an immune-mediated autoimmune disease, characterized by platelet destruction induced by auto antibodies directed against specific glycoproteins of platelet surface, impaired megakaryocyte maturation with reduced platelet production. Accumulating evidence from studies of platelet kinetics also points to the contribution of immune-mediated suppression of megakaryocyte and platelet development in many patients; megakaryocyte apoptosis and suppression of megakaryopoiesis in vitro by ITP plasma or T-cells.ITP is one of the most common clinical bleeding disorders, ITP occurs in approximately one-third of bleeding disorders., its clinical features include petechiae, ecchymoses, mucosa bleeding, menorrhagia,rare visceral hemorrage, even fatal intracranial bleeding. Some patients experience fatigues, apprehension of bleeding, withdraw from important professional activities, and a poor quality of life.Conventional prednisone is the first-line therapy for ITP patients,1.0to1.5mg of prednisone per kilogram of body weight daily for four weeks, approximate70%of ITP patients can achieve response, and only30%of patient can receive sustaining remission. The long-term treatment of prednisone for ITP patients will cause severe side effects, such as Cushing syndrome, hyperglycemia, hypertention, peptic ulcer, infection and mental disorders. Unfortunately, tapering in prednisone dosage or discontinuation causes most ITP patients to relapse. So that it is necessary to develop effective and safe therapeutic regimen for ITP patients, which not only increase platelet count quickly but also achieve a long-term remission and patients could tolerate it.In recent years, treatment of primary immune thrombocytopenia with a short of course of high-dose dexamethasone (HD-DXM) has achieved better therapeutic response. Now HD-DXM regimen has been recommended as the first-line therapy for patients with ITP by west doctors and experts. ITP patients were given a single course of HD-DXM pulse therapy, although the short-term efficacy was very high and less side effects, relapse rate also was high after three months, patients could not receive sustained remission. Multiple courses of HD-DXM pulse therapy were given, treatment cycle is long, patient compliance is poor, glucocorticoid effects will increase again. So far, for the HD pulse therapy, how long interval to administer or whether to give maintenance treatment, there is no unified opinion.The study of this regimen is rare in our country. In our present study, we optimize the regimen, by administering2cycles’high-dose dexamethasone as initial therapy in primary thrombocytopenia and compare with conventional prednisone therapy.Objective:To investigate the efficacy and safety of a schedule of2cycles’ high-dose dexamethasone (HD-DXM) as an initial therapy in adults immune thrombocytopenia (ITP), and compare with conventional dose prednisone therapy.Method:A total of73newly diagnosed ITP patients were divided into2groups randomly. In37patients (Dexamethasone group), oral HD-DXM was administered at40mg/d for4consecutive days, repeated one week later, and then failed to maintain. In the remaining36patients (Prednisone group), prednisone was administered orally at1.0～1.5mg·kg-1·d-1for4weeks, and then gradually tapered. If treatment failure occurred during therapy, other treatment regimens, including splenectomy, Rituximab, CsA, or combined application of immunosuppressive therapy, could be chosen.Results:For short-term efficacy, at the end of1st and second week after treatment, the response rate in Dexamethasone group was significantly higher than that in Prednisone group (67.7%vs.36.1%, P<0.05;78.4%vs.55.6%P<0.05), while at the end of the third week, there was no significant difference between two groups (86.5%vs75.0%, P>0.05), though the response rate in Dexamethasone group remained higher. For long-term effect, at the end of2nd and3rd months of follow-up, the relapse rate in Dexamethasone group was significantly lower than that in Prednisone group (21.9%vs.48.1%, P<0.05,34.4%vs.63.0%, P<0.05),while at the end of1st month of follow-up, there was no significant difference ((18.7%vs.22.2%, P>0.05). In HD-DXM group, the relapse rate in patients whose platelet count was less than100×109/L on day5was significantly higher than those more than100×109/L at the end of third month of follow-up (47.1%vs15.0%, P<0.05). In addition, it is well tolerated and no complications such as severe infection or Cushing syndrome were complained in Dexamethasone group. And in prednisone group, most patients presented Cushing syndrome, some patients complicated with infection.Conclusion1)HD-DXM possesses an advantage over traditional dose prednisone therapy in efficacy and reduces the recurrence rate. High-dose dexamethasone therapy could result in rapider response than prednisone treatment.2) A platelet count of less than100×109/L on day5was associated with a high risk of relapse.3)HD-DXM is well tolerated and safety. Objective:To investigate the efficacy and safety of a schedule of2cycles of high-dose dexamethasone (HD-DXM) as an initial therapy in adults immune thrombocytopenia (ITP),and compare with conventional dose prednisone therapy.Methods:A total of73patients with newly diagnosed ITP were randomly divided into2groups. In37patients (Dexamethasone group), oral HD-DXM was administered at40mg/d for4consecutive days, repeated one week later, and then the patients discontinued treatment. In the remaining36patients (prednisone group), prednisone was administered orally at1.0～1.5mg mg·kg-1·d-1for4consecutive weeks, and then gradually tapered. If treatment failure occurred during therapy, other treatment regimens, including splenectomy, Rituximab, CsA, or combined application of immunosuppressive therapy, could be chosen.Results:For short-term efficacy, at the end of1st and second week after treatment, the response rate in Dexamethasone group was significantly higher than that in Prednisone group (67.7%vs.36.1%, P<0.05;78.4%vs.55.6%P<0.05), while at the end of the third week, there was no significant difference between two groups (86.5%vs75.0%, P>0.05), though the response rate in Dexamethasone group remained higher. For long-term effect, at the end of2nd and3rd months of follow-up, the relapse rate in Dexamethasone group was significantly lower than that in Prednisone group (21.9%vs.48.1%, P<0.05,34.4%vs.63.0%, P<0.05),while at the end of1st month of follow-up, there was no significant difference ((18.7%vs.22.2%, P>0.05). In HD-DXM group, the relapse rate in patients whose platelet count was less than100×109/L on day5was significantly higher than those more than100×109/L at the end of third month of follow-up (47.1%vs15.0%, P<0.05). In addition, it is well tolerated and no complications such as severe infection or Cushing syndrome were complained in Dexamethasone group. And in prednisone group, most patients presented Cushing syndrome, some patients complicated with infection.Conclusion(1)HD-DXM possesses an advantage over traditional prednisone therapy in efficacy and reduces the recurrence rate; high-dose dexamethasone pulse could result in rapider response than prednisone.(2) A platelet count of less than100×109/L on day5in patient (Dexamethasone group) was associated with a high risk of relapse at the end of third month of follow-up.(3) HD-DXM is well tolerated and safety. BackgroundPrimary immune thrombocytopenia (ITP), one of the most common bleeding disorders, is an acquired immune-mediated autoimmune disease. The pathogenic mechanism of ITP is complex, and both accelerated platelet destruction in the reticuloendothelial system and impaired megakaryocyte maturation with reduced platelet production have been proven to contribute to thrombocytopenia.1,2The incidence is nearly30new cases per1million per year. Depending on the severity of the thrombocytopenia, the most common manifestations of ITP range from easy bruising and petechiae, to epistaxis and gingival bleeding and, more rarely, anal, gastrointestinal, or intracranial bleeding.Glucocorticoids are the standard first-line therapy for ITP and most patients achieve a durable response. However, approximately one third of the patients with ITP fail to response to glucocorticoid therapy. These patients often need high doses of glucocorticoids to maintain the therapeutic effects, and these usually cause significant adverse effects. Splenectomy or second-line therapies such as immunosuppressive agents, Rituximab, and recombinant human thrombopoietin (rhTPO) can be chosen for patientswith glucocorticoid treatment failure. Treatments with immunosuppressive agents or Rituximab often require a long treatment course to achieve satisfactory responses.4,5Patients can achieve a rapid response with rhTPO treatment but usually the response is not sustained once the regime was withdrawn, making it difficult to achieve a long-term remission for ITP patients. It has become increasingly important to develop effective therapeutic regimens, which not only increase the number of platelets quickly but also achieve a long-term remission for ITP. In the present study, the efficacy of rhTPO combined with cyclosporin A(CsA) for the treatment of refractory ITP was investigated, and results showed that the short-term and long-term responses in the combination treatment group was better than that in the rhTPO control group. This suggests that combined use of rhTPO and CsA might be an effective alternate regimen for the management of refractory ITP patients. ObjectiveThe management of patients with refractory immune thrombocytopenia is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin (rhTPO) in combination with cyclosporin A (CsA) for the management of refractory ITP patients.MethodsForty-one refractory ITP patients were randomly divided into an observation group and control group. In the observation group, twenty-one patients received subcutaneous injection of rhTPO at a dose of lug/kg (300U/kg) once daily up to day14. Simultaneously they also received oral CsA at a dose of1.5-2mg/kg twice daily for three months. In the control group, rhTPO alone was administered subcutaneously at1ug/kg once daily in the other twenty ITP patients for14consecutive days and then the treatment was withdrawn. If treatment failure occurred or patients relapsed during therapy, other treatment regimens, including splenectomy, Rituximab, or combined application of immunosuppressive therapy, could be chosen.ResultsThere was no significant difference in the response rate at the end of the first week after treatment initiation between the observation group and the control group (61.9%vs.55.5%, x2=0.17, P>0.05), neither was there at the end of the second week(90.5%vs.90.0%, x2=0.22,P>0.05).However, the relapse rate in the observation group was significantly lower than that in control group at the end of the first (15.8%vs.44.4%, x2=3.62, P<0.05), second (26.3%vs.61.1%, x2=5.90, P<0.05) and the third month(31.6%vs.83.3%, x2=10.07, P<0.01). In addition, rhTPO plus CsA were well tolerated and adverse events recorded were mild.Conclusion Combination therapy with rhTPO and CsA was effective in the management of refractory ITP patients, with a relatively short time to response and low recurrence rate, it might be considered as a potential second-line treatment regimen for ITP.