活化单倍相合异基因造血干细胞治疗晚期难治性肾癌的疗效观察

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

目的:探讨活化单倍相合异基因造血干细胞(haplo-HSCs)治疗晚期难治性肾癌的安全性和有效性。方法:10例晚期肾癌患者入组,均接受1个疗程的haplo-HSCs治疗,分别通过影像学检查、生活质量(KPS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:(1)10例患者中,2例部分缓解(PR),6例疾病稳定(SD),2例疾病进展(PD),有效率(CR+PR)为20%,临床获益率(CR+PR+SD)为80%。中位随访时间21个月,中位达进展时间(mTTP)为5.7个月,中位生存时间为16个月,1年生存率为70%。(2)治疗后患者的CD3+、CD4+、CD4+/CD8+、CD3-CD16+56+(NK)均明显升高(P<0.05),而CD8+、CD4+CD25+(Tregs)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:晚期难治性肾癌患者,采用活化haplo-HSCs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 the activated haploidentical allogeneic hematopoietic stem cells （haplo-HSCs）on the advanced intractable renal cell carcinoma （RCC）. Methods： Ten advanced RCC patients were enrolled in this treatment, everyone accepted one cycle of activated haplo-HSCs.The clinical and immunologic responses were evaluated by imaging examination,KPS score, lymphocytes subset and cytokine changes respectively. Results： （1） 2 cases of partial remission（PR）, 6 cases of stable disease （SD）,2 cases of progressive disease（PD） were identified in these ten patients. The total effective rate （CR＋PR） was 20%, the clinical benefit rate （CR＋PR＋SD） was 80%. The median follow-up time was 21 months,the median time to progress was 5.7 months, and the median survival time was 16 months; the one year survival rate was 70%.（2）The proportions of CD3^＋,CD4^＋, CD4^＋/CD8^＋, CD3^-CD16^＋ 56^＋（NK）increased significantly after the treatment （P〈0.05）, but the proportions of CD8^＋, CD4^＋CD25^＋ （Tregs）decreased significantly （P〈0.05）.The levels ofThl cytokine （TNF-α,IFN-γ）obviously increased （P〈0.01）, in contrast the levels of TGF-β decreased（P〈0.05）. （3） Except transient fever and fatigue,no severe adverse events were observed during or after the treatment. Conclusion： The activated haplo-HSCs treatment can enhance the immune function ,elevate the survival rate and quality of life for the advanced intractable RCC patients,and the adverse events are tolerable.