扶正解毒方辨治弥漫大B细胞淋巴瘤免疫逃逸的临床研究

目的:探讨扶正解毒方辨治完全缓解的弥漫大B细胞淋巴瘤的临床疗效及免疫调控效应。方法:100例获得完全缓解的弥漫大B细胞淋巴瘤患者随机分为治疗组和对照组(各50例),对照组患者给予定期观察随访,治疗组在随访基础上给予扶正解毒方。系统分析两组患者1年无进展生存率(progression-free survival,PFS)和总生存率(overall survival,OS),同时采用流式细胞仪和酶联免疫吸附法分别检测并比较两组患者治疗前后外周血T淋巴细胞亚群、淋巴瘤负荷标志物(乳酸脱氢酶、铁蛋白和血β2微球蛋白)水平,治疗组治疗前后血浆血管内皮生长因子(vascular endothelial growth factor,VEGF)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)和干扰素-γ(interferon-γ,IFN-γ)水平,并比较两组患者临床疗效、不良反应。结果:经过1年的随访,治疗组和对照组分别有3例和7例患者脱落。治疗组1年PFS明显高于对照组(分别为97.87%和83.72%,P=0.047),但两组患者1年OS均为100%。治疗组患者外周血CD₃⁺、CD₄⁺、CD₄⁺/CD₈⁺分别为(70.511±12.479)%、(35.900±8.278)%和1.213±0.658,显著高于对照组[(64.867±14.050)%,P=0.047;(32.179±9.117)%,P=0.045;0.916±0.433,P=0.007],治疗组患者CD;淋巴细胞水平显著低于对照组[分别为(30.155±9.632)%和(34.540±10.571)%,P=0.042]。治疗组治疗后血浆乳酸脱氢酶和血β2微球蛋白均显著低于对照组,差异均有统计学意义(P<0.05)。治疗组患者服用扶正解毒方1年后血浆VEGF、TGF-β1和IFN-γ水平与治疗前比较,差异均无统计学意义(P=0.099,P=0.174,P=0.366)。治疗组患者中医证候有效率明显高于对照组(分别为85.11%和60.47%,P=0.030),治疗组患者未发生治疗相关不良反应事件。结论:扶正解毒方可以提高缓解后弥漫大B细胞淋巴瘤患者的1年PFS及降低肿瘤负荷,并改善其中医证候,其机制可能与其调控T淋巴细胞亚群和免疫相关因子进而阻断肿瘤免疫逃逸有关。

Clinical Study on Fuzheng Jiedu Recipe in Treating Diffuse Large B-cell Lymphoma Immune Escape

Objective:To investigate the clinical efficacy and immunoregulatory effects of Fuzheng Jiedu Recipe in treatment of diffuse large B-cell lymphoma(DLBCL)in complete remission.Methods:100 DLBCL patients who achieved complete remission were randomly divided into a treatment group and a control group(50 cases each).The control group received regular observation and follow-up,and the treatment group was given Fuzheng Jiedu decoction on the basis of follow-up.One-year progression free survival(PFS)and overall survival(OS)were systemically compared and analyzed between two groups.Meanwhile,Flow cytometry and ELISA assay were used to analyze changes of immune function markers including T lymphocyte subsets,biomarkers of tumor burden(lactic dehydrogenase,β2-microglobulin and ferritin),as well as plasma levels of vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1)and Interferon-γ(IFN-γ).The clinical efficacy and adverse reactions of the two groups of patients were compared.Results:After 1 year of follow-up,there were 3 and 7 patients fell out from treatment and control group,respectively.The 1-year OS of DLBCL patients in both groups was 100%,while the 1-year PFS of patients in treatment group was significantly higher than those in the control group(97.87%vs 83.72%,P=0.047).The levels of peripheral CD₃⁺ and CD₄⁺ T lymphocytes as well as ratio of CD₄⁺/CD₈⁺ lymphocytes were 70.511±12.479%,35.900±8.278%and 1.213±0.658,respectively,which were significantly higher than those in the control group(64.867±14.050%,P=0.047;32.179±9.117%,P=0.045;0.916±0.433,P=0.007).Moreover,the levels of peripheral CD₈⁺ lymphocytes were significantly lower than that in control group(30.155±9.632%vs 34.540±10.571%,P=2.242).After treatment,plasma lactate dehydrogenase and bloodβ2 microglobulin in the treatment group were significantly lower than those in the control group,and the differences were statistically significant(P<0.05).The plasma VEGF,TGF-β1 and IFN-γlevels of patients in the treatment group after taking Fuzheng Jiedu Decoction for 1 year were compared with those before treatment,and there was no significant difference(P=0.099;P=0.174;P=0.366).The effective rate of TCM syndromes in the treatment group was significantly higher than that in the control group(85.11%and 60.47%,respectively,P=0.030),and no treatment-related adverse events occurred in the treatment group.Conclusion:Fuzheng Jiedu Recipe can increase the 1-year PFS and reduce tumor burden in DLBCL patients after remission,and improve the Chinese medical syndromes.Its mechanism may be related to the regulation of T lymphocyte subsets and immune-related factors to block tumor immune escape.