含胸腺肽增强免疫的自体CIK细胞输注联合小剂量IL-2方案治疗老年人B-CLL的近期疗效观察  

Short-term Curative Efficacy of Autologous Cytokine Induced Killer Cells Combined with Low-dose IL-2 Regimen Containing Immune Enhancement by Thymic Peptide in Elderly Patients with B-Cell Chronic Lymphocytic Leukemia

作　　者：蔡力力[1] 杨洋[2] 杨波[2] 朱宏丽[2] 卢学春[2] 张文英[2] 于睿莉[3] 迟小华[4] 王瑶[5] 代汉仁[5] 韩为东[5] 范辉[2] 李素霞[2] 刘洋[2] 冉海红[2] 林洁[1] 脱帅[6] 脱朝伟[6] 张峰[7] 曹军平[8] 姚善谦[2] 

机构地区：[1]解放军总医院南楼临床检验科,北京100853 [2]解放军总医院南楼血液科,北京100853 [3]解放军总医院耳鼻咽喉研究所,北京100853 [4]解放军第二炮兵总医院药剂科,北京100800 [5]解放军总医院基础研究所免疫室,北京100853 [6]解放军第202医院医务处,辽宁沈阳110003 [7]中国科学院北京基因组研究所,北京100029 [8]武警总医院供应室,北京100853

出　　处：《中国实验血液学杂志》2012年第3期564-570,共7页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号30772597;30873086;81172986);解放军总医院科技创新苗圃基金(编号11KMM24;11KMM23);中国博士后科学基金(编号20080431362);中央保健研究基金(编号B2009B115);科技部新药创制重大专项(编号2008ZXJ09001-019)

摘　　要：本研究评价含胸腺肽增强免疫的自体细胞因子诱导的杀伤细胞(CIK)输注联合小剂量IL-2方案治疗老年人B细胞性慢性淋巴细胞白血病(B-CLL)的安全性及疗效。以胸腺肽α1作为增强免疫方案,用法为1.6 mg/d,皮下注射,14 d为1个周期。采集5例B-CLL老年患者外周血单个核细胞,每周采集1次,分别在应用胸腺肽α1前和应用1个周期后各采集3次,在体外经干扰素-γ(IFN-γ)、白介素-2(IL-2)及抗CD3单克隆抗体诱导成CIK细胞,观察对比应用胸腺肽α1前后CIK细胞在扩增数量、效应细胞扩增倍数、淋巴细胞亚群比例及体外杀瘤活性的变化。5例患者在接受胸腺肽α1治疗后开始进行自体CIK细胞联合小剂量IL-2方案免疫治疗,具体为:胸腺肽α1 1.6 mg/d,皮下注射,隔日1次;每次回输CIK细胞数为(4-6)×109个,回输后应用IL-2 1 mU/d,皮下注射,第1-10天。28 d为1个疗程,动态观察CIK细胞治疗前后细胞免疫功能、肿瘤相关生物学指标、疾病缓解情况及感染频次、程度的变化。结果表明:胸腺肽α1增强免疫治疗后体外诱导CIK细胞在扩增数量、效应细胞扩增倍数、比例及体外杀瘤活性4个方面均明显高于胸腺肽α1治疗前(P<0.05)。5例患者共接受46个疗程的CIK细胞联合IL-2治疗,未观察到明显不良反应。治疗后5例患者一般情况得到不同程度改善,CD3+、CD3+CD8+、CD3+CD56+细胞比例明显升高(P<0.05),血清β2微球蛋白水平显著下降(P<0.05),感染频次减少,程度减轻(P<0.05);3例由部分缓解(PR)达到完全缓解,1例由疾病稳定(SD)达到PR,1例由疾病进展达到SD。结论:含胸腺肽增强免疫的自体CIK细胞联合小剂量IL-2方案治疗老年人B-CLL安全有效。This study was purposed to evaluate the safety and curative effect of autologous cytokine induced killer cells（CIK） combined with low-dose IL-2 regimen containing immune enhancement of thymic peptide on elderly patients with B-cell chronic lymphocytic leukemia（B-CLL）.Thymic peptide α1 was subcutaneously given as the immunoenhancement agent at a dose of 1.6 mg/d,14 days as one cycle.Peripheral blood mononuclear cells（PBMNC） from 5 patients with B-CLL were isolated once a week to induce ex vivo CIK cells through culture in the context of interferon（IFN）-γ,interleukin（IL）-2 and anti-CD3 monoclonal antibody.The PBMNC were separated from patients before and after 14 days as one cycle of thymic peptide α1 administration.Parameters of amplification ability,effector cells quantity,lymphocyte subgroups percentage and antitumor cytotoxicity were compared before and after thymic peptide administration.The 5 patients were treated with CIK cells combined with low-dose IL-2 regimen immediately after injection of thymic peptide α1.The CIK cells plus low-dose IL-2 regimen containing thymic peptide enhancement was defined as： thymic peptide α1 1.6 mg/d was subcutaneously administered once every other day;（4-6）×109 of CIK cells were transfused followed by IL-2 subcutaneous administration of 1 mU/d on days 1-10,28 days as one cycle.Clinical evaluation parameters including cellular immunity function,CLL related biomarkers,disease state and infectious frequency and degree were investigated before and after CIK cells infusion puls IL-2.The results showed that the amount of amplified CIK cells,the percentage and amplification times of effector cells and antitoumor cytotoxicity more significantly increased after thymic peptide α1 treatment than before its use（P〈0.05）.The total 46 cycles of CIK cells infusion plus IL-2 were completed in the 5 CLL patients.No adverse reaction was observed.After treatment of CIK cells plus IL-2,the general conditions of 5 CLL patients were to different extent improved

关 键 词：细胞因子诱导的杀伤细胞 胸腺肽 白介素2 慢性淋巴细胞白血病 B细胞性 老年人 

分 类 号：R733.72[医药卫生—肿瘤] R979.1[医药卫生—临床医学]