硼替佐米在复发／难治免疫性血液病中的应用

Bortezomib in treatment of patients with relapsed/refractory autoimmune hematological disease

复发/难治免疫性血液病，指由机体免疫功能紊乱引起的，以自身抗体介导为主，以血细胞或血浆蛋白质破坏为特征，并且对传统免疫抑制治疗方案（皮质类固醇激素、免疫抑制剂等）效果不佳的血栓与出血性疾病，病情严重时可危及患者生命，后续治疗相当困难。为提高该类患者生存率及改善其远期预后，探寻新的有效治疗方法具有一定临床挑战性。硼替佐米作为唯一应用于肿瘤临床治疗的蛋白酶体抑制剂，既往在多发性骨髓瘤（MM）的治疗中取得较好临床效果。以硼替佐米为代表的蛋白酶体抑制剂在诱导浆细胞凋亡、影响抗原加工、抑制自身反应性T细胞增殖、减少炎症因子产生等免疫调节通路的多方面中发挥一定作用，该药物的上述特点为其应用于复发/难治免疫性血液病的治疗提供了临床可行性。近年来，国外部分研究结果表明，针对复发/难治免疫性血液病患者，硼替佐米可以起到挽救性治疗效果。因此，笔者针对这一方面的相关进展进行综述。

Relapsed/refractory autoimmune hematological diseases, belong to the thrombus and hemorrhagic disease, are characterized by autoantibody-mediated blood cells or plasma protein destruction caused by the disorder of the immune system, which have poor responses to conventional immunosuppression, including corticosteroids, immunosuppressive agents etc.. Severe illness can endanger the patient′s life and follow-up treatment is difficult. It is still a clinical challenging to explore new treatments to improve the survival rate and long term prognosis of this type of patients. Bortezomib as the only proteasome inhibitor applied to the clinical treatment of tumors has achieved good clinical results in the treatment of multiple myeloma （MM）. In addition, proteasome inhibitor such as bortezomib, demonstrating pleiotropic immunomodulatory effects, including inducing apoptosis of plasma cells, influencing process of antigen cells, inhibiting proliferation of autoreactive T cells and reducing expression of inflammatory cytokines. These diverse effects have provided the feasibility for the utility of proteasome inhibitor as a salvage therapy for relapsed/refractory autoimmune hematological diseases. In recent years, some foreign studies have shown that bortezomib can be used as a salvage treatment for patients with relapsed/refractory auto immune hematological diseases. Therefore, the article summarizes the recent research progress of proteasome inhibitor treatment in relapsed/refractory autoimmune hematological diseases.