HLA半相合外周血活化干细胞治疗晚期实体瘤的疗效  

Clinical efficacy of activated-HLA haploidentical peripheral blood stem cells in treatment of advanced solid tumors

作　　者：韩颖[1,2] 于津浦[2] 李慧[2] 任宝柱[2] 曹水[2] 张迺宁[2] 安秀梅[2] 任秀宝[2] 

机构地区：[1]辽宁医学院,辽宁锦州121001 [2]天津市肿瘤防治重点实验室天津医科大学附属肿瘤医院生物治疗科,天津市300060

出　　处：《中国肿瘤生物治疗杂志》2010年第1期7-12,共6页Chinese Journal of Cancer Biotherapy

基　　金：国家"十五"科技攻关引导项目资助(No.2005BA740C);天津市科技创新项目资助(No.06FZZDSF01500)~~

摘　　要：目的:观察HLA半相合外周血活化干细胞(HLA haploidentical peripheral blood stem cells,haplo-PBSCs)对晚期难治性实体瘤患者的临床抗肿瘤疗效以及不良反应。方法:入组42例全部为2004年10月至2007年10月天津医科大学肿瘤医院生物治疗科收治的晚期难治性恶性肿瘤患者(所有入组患者均知情同意,试验工作经医院伦理委员会批准),其中卵巢癌12例,肾癌9例,肺癌8例,乳腺癌8例,结肠癌2例,胃癌2例,恶性黑素瘤1例。供者为患者健康直系亲属,进行haplo-PB-SCs的动员、采集和体外rhIL-2活化。经HLA半相合外周血干细胞治疗后,分别通过CT/PET-CT检查、RESIST标准、KPS评分、临床症状缓解率等指标来评估HLA半相合外周血干细胞的临床疗效及不良反应情况。结果:42例患者接受1个疗程治疗后,全体患者中位无进展生存期(PFS)为6个月,临床获益率(CR+PR+SD)为73.8%;患者生活质量总获益率为76.2%,生活质量评分(KPS)较治疗前平均提高20分(0～30分)。其中,KIR不相合方向为GVH组的临床获益率、无进展生存期、生活质量总获益率均显著优于HVG(或相合)组[94.1%vs60.0%,(13.4±1.3)vs(8.0±0.9)个月,89.5%vs65.2%,均P<0.05];供受者关系为母子/女组的治疗有效率、患者生存期和生活质量均显著优于父子/女组(均P<0.05);肾癌和卵巢癌的临床获益率分别为90.0%和81.8%,相对于其他类肿瘤类型高,在治疗反应性和敏感性上可能占优势。结论:HLA半相合外周血活化干细胞治疗后,机体产生非特异性的抗肿瘤作用,对改善患者症状和提高生活质量有显著效果。Objective：To evaluate the anti-tumor and side effects of activated-HLA haploidentical peripheral blood tem cells （haplo-PBSCs） in the treatment of advanced refractory solid tumor patients.Methods：Forty-two patients with advanced refractory tumor,who were diagnosed in our hospital from Oct.2004 to Oct.2007,were enrolled in this study （all patients signed informed consent）,including 12 with ovarian cancer,9 with renal cancer,8 with lung cancer,8 with breast cancer,2 with colon cancer,2 with gastric cancer,and 1 with melanoma.The donors were healthy direct relatives of the patients;the donors＇ haplo-PBSCs were mobilized,collected,and activated by rhIL-2 in vitro.The clinical efficacy and side effects of haplo-PBSCs therapy were assessed by CT/PET-CT scanning,RESIST standard,KPS score,and clinical response rates,etc.Results：All 42 patients received one episode of haplo-PBSCs treatment.The progression-free survivals （PFS） were 6 months and the clinical beneficial rate （CR＋PR＋SD） was 73.8%.The beneficial rate of life quality was 76.2% and the KPS increased by 20 （0-30） points on average after haplo-PBSCs treatment.The patients with KIR unmatched in GVH direction had better outcomes than those with KIR matched or KIR unmatched in HVG direction （P〈0.05）,and the clinical beneficial rate,PFS and total beneficial rate were 94.1% vs 60.0%,（13.4±1.3） vs （8.0±0.9） months,and 89.5% vs 65.2%,respectively （all P〈0.05）.The donor/recipient relation as the mother/child had a better outcome than that as the father/child （P〈0.05）.Patients with renal cancer or ovarian cancer had better outcomes than those with other cancers,with clinical beneficial rates being 90.0% and 81.8%,respectively.Conclusion：Activated haplo-PBSCs therapy can induce non-specific anti-tumor effect,and improve the clinical symptom and life quality of advanced tumor patients.

关 键 词：晚期实体肿瘤 HLA半相合 外周血活化干细胞 免疫治疗 

分 类 号：R730.54[医药卫生—肿瘤]