IL-2/GM-CSF体外处理的自体外周血单个核细胞治疗再生障碍性贫血131例临床研究  

Clinical study on autologous peripheral mononuclear cells treated by IL-2 and GM-CSF in culture in the treatment of 131 patients with aplastic anemia

作　　者：詹昱[1] 陈玲珍[1] 曲佳[1] 谭雪芳[1] 冯可欣[1] 巫进明[1] 杨郁青[1] 谭明珠[1] 罗英[1] 杨德懋[1] Zhan Yu;Chen Lingzhen;Qu Jia;Tan Xuefang;Feng Kexin;Wu Jinming;Yang Yuqing;Tan Mingzhu;Luo Ying;Yang Demao(Department of Hematology,Guangzhou Twelfth People＇s Hospital,Guangzhou 510620,China)

机构地区：[1]广州市第十二人民医院血液科,510620

出　　处：《国际医药卫生导报》2018年第21期3219-3223,共5页International Medicine and Health Guidance News

基　　金：广东省医学科学技术研究基金项目（A2017499）

摘　　要：目的观察IL-2/GM-CSF体外处理的自体外周血单个核细胞治疗再生障碍性贫血（Aplastic Anemia,AA）患者的疗效和安全性.方法选取2003年10月至2016年5月在本院住院或门诊随访的131例获得性原发性AA患者,中位年龄26（2～77）岁,重型AA71例,非重型AA60例.92例（70.2%）曾接受免疫抑制治疗,均无效或不能耐受.取自体外周血单个核细胞,在IL-2、GM-CSF等作用下培养48h后进行静脉输注,每周1～2次,根据疗效及不良反应决定输注疗程.结果131例患者接受细胞输注中位60（15～160）次,中位治疗时间14（3～43）个月,中位随访时间26（4～150）个月.30例（22.9%）完全反应,74例（56.5%）部分反应,总有效率79.4%;27例（20.6%）无效.治疗有效患者从细胞治疗开始到脱离输血、网织红细胞〉20×109/L、Hb增长30g/L以上、ANC〉0.5×109/L、PLT〉20×109/L以及获完全反应的中位时间分别是5（1～21）个月、4（1～16）个月、11（3～27）个月、12（6～25）个月、9（2～35）个月、27（10～56）个月.83例（63.4%）患者在治疗前CD4＋/CD8＋细胞比值倒置（〈1）,治疗后66例不同程度升高,其中55例均为治疗有效患者.部分患者细胞输注过程中出现短暂寒战、发热,无其他治疗相关性不良反应.结论IL-2/GM-CSF体外处理的自体外周血单个核细胞输注有助于改善AA患者的骨髓造血功能,纠正T淋巴细胞功能紊乱,临床观察未发现发热以外的其他不良反应.Objective To explore the effcacy and safety of autologous peripheral mononuclear cells treated by IL-2 and GM-CSF in culture in the treatment of aplastic anemia （AA）. Methods 131 patients with primary AA were enrolled with median age of 26 （2~77） years old, including 71 cases of severe AA, and 92 cases of whom （70.2%） were cyclosporine and anti-thymocyte globulin-resistant or unacceptable. Autologous peripheral mononuclear cells were isolated and cultured for 48 hours in presence of IL-2 and GM-CSF and successively administered intravenously to patients once or twice a week. The treatment course was determined by the effcacy and the adverse reactions. Results After a median of 60 times （15-160 times） of cell infusion, 14 months （3-43 months） of duration, and 26 months （4-150 months） of follow-up, the total response rate was 79.4%, including complete response （CR） in 30 cases （22.9%）, partial response （PR） in 74 cases （56.5%）, and non-response in 27 cases （20.6%）. The median treatment duration for transfusion independence, granulophilocyte 〉20×109/L, increase of haemoglobin 〉30 g/L, neutrophils 〉0.5×109/L, platelets 〉20×109/L, and access to CR were respectively 5 （1-21）months, 4 （1-16） months, 11 （3-27） months, 12 （6-25） months, 9 （2-35） months, and 27 （10-56） months in patients with response. Sixty-six cases of 83 patients recovered from inverted ratio of CD4＋/CD8＋ cells and 55 of whom were effective cases. A small number of patients had transient chills and fever during or after cell infusion, there were no other treatment-related side effects observed. Conclusion The therapy described appears to effective and safe for the treatment of AA in our preliminary study, and a larger, controlled study is warranted.

关 键 词：再生障碍性贫血 白介素-2 粒细胞-巨噬细胞集落刺激因子 单个核细胞 

分 类 号：R556.5[医药卫生—血液循环系统疾病]