树突状免疫细胞疗法治疗再生障碍性贫血的临床初步探讨  

Clinical observation of immunotherapy in patients with aplastic anemia

作　　者：高飏[1] 肖扬[1] 旁妍[1] 蒋祖军[1] 肖浩文[1] 杨德懋[2] 王晓怀[3] 

机构地区：[1]广州军区广州总医院血液科,广州510010 [2]广州军区广州总医院医学实验科 [3]广州军区广州总医院肿瘤科

出　　处：《临床血液学杂志》2009年第3期249-252,共4页Journal of Clinical Hematology

基　　金：广州市重大科技项目(No:2003A3020301);广东省自然基金(No:5000138)

摘　　要：目的：探讨树突状细胞为主的免疫细胞疗法治疗再生障碍性贫血（AA）的疗效及安全性。方法：选择抗胸腺细胞免疫球蛋白／抗淋巴细胞免疫球蛋白（ATG／ALG）或环孢菌素（Cs-A）治疗无效、HLA配型失败的AA患者共38例，分离其外周血单个核细胞（MNC），体外培养48h后收集形成的新免疫细胞，洗涤后经静脉回输患者，每疗程后检测患者外周血常规、骨髓象及骨髓活检，流式细胞检测治疗前后外周血T细胞亚群CD4^＋，CD8^＋，CD69^＋水平及CD3^＋、CD8^＋细胞内γ干扰素（IFN-γ），α-肿瘤坏死因子（TNF-α）表达。结果：38例AA患者外周血MNC经体外细胞因子及钙离子载体混合培养后，均分化成以树突状细胞为主的新型免疫细胞，27例（71％）患者经此种激活的免疫细胞治疗2个疗程后骨髓象、骨髓活检发生显著改变；29例（76．3％）患者在治疗4个疗程后临床症状明显改善，血常规、CD4／CD8比值均较治疗前显著进步；基本治愈6例（15．8％），缓解8例（21％），明显进步12例（31．6％）；总有效率68．4％，疗效与Cs—A组接近；治疗后CD3^＋、CD8^＋细胞内IFN-γ明显降低；除部分患者（52．6％）有一过性寒战发热外，未发现明显不良反应；随访6～18个月无复发病例。结论：以树突状细胞为主的免疫细胞对AA患者的骨髓造血及免疫功能具有一定调节作用，临床应用安全、有效。Objective：To observe the clinical effect and safety of immunotherapy in patients with aplastic anemia （AA）. Method：Subjects were 38 AA patients, who were failure to treatment with ATG/ALG and Cs-A or had no HLA matched donors. We isolated the mononuclear cells from blood, cultured there cells with IL-2, GM-CSF and calcium ion carrier（CI）, observed the cells morphology by inverted microscope, and measured the immunal markers by flow cytometry. At last, these collected cells were transfused to these patients. Blood cells count, bone marrow morphology examinations and histopathology examinations were taken every 3 months. CD4^＋, CD8^＋ , CD69^＋ T lymphocytes in peripheral blood, TNF-α and IFN-γ in peripheral blood and in CD3^＋ , CD8^＋ T lymphocytes were measured before and after immunotherapy by flow cytometry. Result： Of 38 AA patients, 27 （71 %） obtained improved hematopoietic function by bone marrow morphology and histopathology examinations after 2 courses; 29 （76.3 % ） got improved clinical manifestation after 4 courses. Significantly elevated levels of blood cells count, the ratio of CD4 to CD8 were found. 6（15.8%） cured, 8（21%） relieved, 12（31.6%） improved obviously, the total effective rate were 68.4%, and got close to ciclosporin group. In immunotherapy group. Intracellular IFN-γin PB CD3^＋ , CD8^＋ T lymphocytes of AA patients after immunotherapy for more than 6 months was significantly lower compared with before. In immunotherapy group, only 52.6% patients showed shiver and fever at primary phase and no other side effect was observed. There is no relapse during following-up for 6- 18 months. Conclusion：The immunotherapy can regulate the immune and hemopoietic function of patients with AA. Clinical application of this method showed good safety and effect.

关 键 词：免疫细胞 贫血 再生障碍性 治疗 

分 类 号：R556[医药卫生—血液循环系统疾病]