Recombinant Human Thrombopoietin (RhTPO)Combinating Rituximab Therapy For Immune Thrombocytopenia (ITP)

BackgroundImmune Thrombocytopenia (ITP) is an acquired autoimmune disorder that characterized by a decrease in the number of circulating platelets and increases the risk of bleeding events.The decrease of platelets is resulted from antibody-and cell-mediated destruction of platelets and suppression of platelet production. Recombinant human Thrombopoietin (rhTPO) is a glycosylated protein produced in Chinese hamster ovary (CHO) cells consisting of the full-length, native human amino acid sequence,. rhTPO is involved in nearly every step of megakaryocyte development,It stimulates megakaryocyte maturation and platelet release.It works fast, but the platelet count rebound easily after discontinuation. Rituximab is a chimeric monoclonal antibody directed against the CD20antigen present on B lymphocytes. So rituximab can deplete B cells and inhibit the production of antibody.It works slowly,but has long duration. To sum up, rhTPO and rituximab are complementary in mechanism and effect time window.ObjectiveTo investigate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combinating low-dose rituximab in management of steroid-resistant/relapsed immune thrombocytopenia.MethodsTotally40steroid-resistant/relapsed ITP patients enrolled. All the subjects received rhTPO at the dose of300IU·kg-1daily in14consecutive days,then the treatment frequency depended on the platelet count (A target platelet count was above50×109/L). Withdrawal could be performed on day29.Low-dose rituximab (100mg ivdrip)was administered weekly(on day1,8,15,22). All the subjects had being observed in the hospital for22days and then followed up monthly for2months.ResultsA complete response(platelet count s≥100×109/L and absence of bleeding) was achieved in23cases, a response(platelet count≥30×109/L and at least2-fold increase the baseline count and absence of bleeding)in32cases, and no response (platelet count <30×109/L or less than2-fold increase of baseline)in8cases.16patients of those respondors was followed up monthly for2months,5cases relapsed(platelet count below30×109/L or bleeding from CR or R).The median time to response was7days.Median response duration was12weeks.Treatment had no significant influence on blood pressure, breathing, pulse, electrocardiogram,WBC,HGB, Liver and kidney function,blood clotting. Adverse effects were slight.ConclusionThe combination of rhTPO and low-dose rituximab is an effective and safty option in management of steroid-resistant/relapsed ITP for high response rate,rapid effect and slight adverse effects.