An Inveatigation Of Recombinant Human Interleukin-11Combinating Low-dose Rituximab In Management Of Primary Immune Thrombocytopenia

Primary immune thrombocytopenia (ITP) is a hemorrhagic disease with isolated peripheral blood thrombocytopenia due to platelet immune destruction. ITP is characterized with extensive skin and mucosal hemorrhage, peripheral thrombocytopenia, reduced platelet survivals, normal or increased megakaryocyte numbers in bone marrow. The etiology and pathogenesis of ITP is unknown, its etiology may be related to infection, immune factors, the role of the spleen and genetic factors. The current study found that the pathogenesis involved the complex relationship among T cells, B cells, megakaryocytes and cytokines.Interleukin-11(IL-11) is a unique thrombopoietic growth factor which causes proliferation of megakaryocyte progenitors as well as induces megakaryocytic maturation. Domestic scholars have made some progress in the application of rhIL-11treatment for chronic refractory ITP. Because of its B-cell depleting effect, Rituximab has entered clinical trials in several autoimmune conditions. The common standard dosage is375mg/m2qw×4, but the cost is relatively high. Foreign researches have displayed the efficiency of standard Rituximab treatment is around60%.Objective:To evaluate the efficacy and safety of recombinant Human Interleukin-11(rhIL-11) combinating low-dose Rituximab in management of steroid-resistant/relapsed Immune Thrombocytopenia (ITP).Methods:Twenty-three steroid-resistant/relapsed ITP patients were enrolled in the study. rhIL-11was given at3mg/d, ih, for14days; Rituximab was given at100mg, ivdrip, on the first, eighth, fifteenth, twentieth day, respectively. The effect was evaluated into CR, R and NR.Results:The effect was evaluated in18patients. After the beginning of treatment, the median platelet counts increased from16.5(4.0—50.0)×109/L to27.5(9.0-191.0)×109/L,34.5(13.0-269.0)×109/L,58.0(17.0-290.0)×109/L,67.0(10.0-308.0)×109/L,68.5(18.0-326)×109/L,112.5(8.0-277.0)×109/L and80.0(12.0-260.0) on the fourth, seventh,eleventh, fourteenth, eighteenth and twenty-second day, respectively. After the discontinuation of treatment, the platelet count decreased gradually. On the third month, the median platelet count was87.0(8.0-230.0)×109/L, which was still significantly higher than the level before the treatment(P<0.01). The rate in the group with CR was10/18(56%) and that in the R group was4/18(22%). The overall response rate was77.8%.5patients relapsed, and needed further treatment. Only3patients had mild clinical untoward reactions.Conclusions:Treatment with recombinant Human Interleukin-11(rhIL-11) combinating low-dose Rituximab may be an effective and safe approach in patient with steroid-resistant/relapsed Immune Thrombocytopenia (ITP), and adverse reactions are mild. However, the optimal therapeutic schedule, long-term efficacy, adverse events need to further investigation.