细胞因子诱导的免疫细胞治疗苯中毒再生障碍性贫血的临床研究  

Clinical study on treatment of aplastic anemia caused by benzene using cytokine induced immune cells

作　　者：刘薇薇[1] 陈嘉榆[2] 余卫[2] 杨志前[1] 杨德懋[2] 张程[1] 刘移民[3] 

机构地区：[1]广州市第十二人民医院职业病科,广东广州510620 [2]广州市第十二人民医院血液病科,广东广州510620 [3]广州市第十二人民医院科技委员会,广东广州510620

出　　处：《中国工业医学杂志》2010年第1期13-17,共5页Chinese Journal of Industrial Medicine

基　　金：广东省医学科学技术研究基金(编号:A2003674)

摘　　要：目的评价细胞因子诱导的免疫细胞治疗苯中毒致再生障碍性贫血的临床疗效及安全性,并探讨其可能机制。方法我院2001年3月至2007年2月所收治的25例确诊苯中毒致再生障碍性贫血患者,经院伦理委员会批准和患者知情同意后,接受了此项治疗。抽取患者外周血40-50 ml,分离单个核细胞,经白细胞介素-2、粒细胞巨噬细胞集落刺激因子（GM-CSF）混合培养6 d,收集形成的新免疫细胞并清除杂质后,静脉回输给患者,每周一次,平均16次;观察其近期临床疗效、免疫学活性及不良反应等。并随访追踪观察。结果（1）25例患者经治疗后,基本治愈16例,缓解4例,明显进步4例,无效1例,有效率达96%,未出现严重不良反应,随访最长7年6个月,无复发和死亡病例。（2）单因素相关分析显示,治疗前,患者骨髓的巨核细胞数、骨髓增生程度和外周血WBC值高低与外周血中T辅助细胞（CD4＋）比例正相关,而骨髓非造血细胞比例与CD4＋比例负相关（P均〈0.05）;Hb含量与T抑制细胞（CD8＋）负相关（P〈0.05）;治疗后,上述相关关系均消失（P〉0.05）。（3）多因素逐步回归分析可见,治疗前,骨髓的增生程度、外周血WBC和PLT数与CD4＋比例正相关;治疗后,PLT数受CD8＋比例的影响。结论机体T细胞免疫功能紊乱可能是苯中毒再障的一个不可分割的重要环节,细胞因子激活的免疫细胞能诱导机体产生特异性的免疫反应,对治疗苯中毒再障具有较高的临床价值。Objectives To assess the therapeutic effect and safety of immune cells induced by cytokines on benzene caused aplastic anemia,and explore its possible mechanism.Methods Twenty-five patients with aplastic anemia caused by benzene were admitted to our hospital during 2001 to 2007 and accepted the therapy of induced immune cells after the informed consent of patients and the approval of Hospital Ethics Committee.The mononuclear cells（MNS）were separated from 40～50 ml peripheral blood of the patients,and cultured with interleukin-2 and granulocyte macrophage clone stimulating factor（GM-CSF）for six days.To collect the immunocytes and transfuse to the patients,once a week for 16 weeks or more,then the therapeutic effect,immunocyte count and adverse reaction were observed.Results It showed that（1）16 patients were basically cured,4 patients relieved,4 patients improved,only 1 patient was ineffective,no obvious adverse reaction,recurrence or death was seen;（2）Before treatment,the megakaryocyte count,bone marrow proliferation degree and peripheral WBC count were positively correlated with the percentages of CD4＋ cells（P0.05）,while the non-hematopoietic cells in bone marrow was negatively correlated with the percentage of CD4＋ cells（P0.05）,and Hb was negatively correlated with percentages of CD8＋ cells（P0.05）.After treatment,these relationships mentioned above were all disappeared（P0.05）according to the one-factor correlation analysis.（3）The multiple factor gradual regressive analysis showed that before treatment,the degree of bone marrow growth,the counts of peripheral WBC and PLT were all positively correlated with CD4＋ cells;while after treatment,only peripheral PLT count was correlated with CD8＋ cells.Conclusion The results suggested that dysfunction of T lymphocyte immune system may play an important role in aplastic anemia caused by benzene;while immune cells induced with cytokines could activate the specific immune response,thereby possessing clinical values in treatment

关 键 词：苯中毒 再生障碍性贫血 免疫细胞治疗 细胞因子 

分 类 号：R135.12[医药卫生—劳动卫生]