活化单倍相合异基因造血干细胞治疗晚期难治性肿瘤的初步观察  

Efficacy of activated haploidentical allogeneic hematopoietic stem cells on advanced intractable carcinoma

作　　者：王运良[1] 康红刚[1] 于津浦[1] 曹水[1] 任宝柱[1] 张新伟[1] 张维红[1] 韩颖[1] 任秀宝[1] 

机构地区：[1]天津医科大学附属肿瘤医院生物治疗科,300060

出　　处：《中国医药生物技术》2008年第6期404-408,共5页Chinese Medicinal Biotechnology

基　　金：国家"十五"科技攻关计划(2005BA740C)

摘　　要：目的探讨活化单倍相合异基因造血干细胞(allogeneic haploidentical hematopoietic stem cells,haplo-HSC)治疗各类晚期难治性肿瘤的安全性和临床疗效。方法42例晚期转移性或化疗抵抗性肿瘤患者入组,均接受一个疗程haplo-HSC治疗,分别通过影像学检查、生活质量评分以及外周血淋巴细胞亚群、细胞因子变化情况来评估临床疗效和免疫学反应。结果①42例患者中,7例部分缓解(PR),25例疾病稳定(SD),10例疾病进展(PD),有效率(CR+PR)为16.67%,临床获益率(CR+PR+SD)为76.19%。中位随访时间21个月,中位达进展时间(mTTP)为3.7个月,中位生存时间为7.8个月,1年生存率为14%;②治疗后患者的CD3+、CD4+、CD4+/CD8+、CD3–CD16+CD56+NK均明显升高(P<0.05),而CD8+、CD4+CD25+Treg明显降低(P<0.05);TNF-α、IFN-γ等Th1类细胞因子明显升高(P<0.01),而TGF-β明显下降(P<0.05);③除一过性的发热、乏力外,未出现其他不良反应。结论晚期难治性肿瘤患者,采用活化haplo-HSC治疗可以增强自身免疫功能,提高生存率和生活质量,并且有良好的耐受性。Objective To evaluate the clinical efficacy and safety of activated haploidentical allogeneic hematopoietic stem cells （haplo-HSC） on advanced intractable carcinoma. Methods Forty-two advanced metastatic or chemoresistant carcinoma patients were enrolled in this trial. Every subject received one cycle of activated haplo-HSC. The clinical and immunologic responses were evaluated by imaging examination, KPS score, lymphocytes subset and cytokine changes respectively. Results （1）Seven cases of partial remission （PR）, 25 cases of stable disease （SD） and 10 cases of progressive disease （PD） were identified. The total effective rate （CR ＋ PR） was 16.67% and the clinical benefit rate （CR ＋ PR ＋ SD） 76.19%. The median follow-up time was 21 months, median time to progress 3.7 months and median survival time 7.8 months; the one-year survival rate was 14%; （2）The levels of CD3＋, CD4＋, CD4＋/CD8＋, CD3-CDI6＋CD56＋ NK increased significantly after treatment （P 〈 0.05）, but CD8＋, CD4＋ CD25＋ Treg decreased significantly （P 〈 0.05）; Thl cytokine （TNF〈t, IFN-y） obviously increased （P 〈 0.01） while TGF-I3 decreased （P 〈 0.05）; （3）Except for transient fever and fatigue, no severe adverse event occurred during or after treatment. Conclusions The activated haplo-HSC could enhance the immune function, boost the survival rate and QOL for patients with advanced intractable carcinoma. Moreover, the tolerance was excellent.

关 键 词：肿瘤转移 造血干细胞 免疫疗法 

分 类 号：R730.5[医药卫生—肿瘤]