自体外周血干细胞移植联合利妥昔单抗治疗弥漫大B细胞淋巴瘤及相关因子的表达

Rituximab combined with autologous peripheral blood stem cell transplantation in the treatment of diffuse large B-cell lymphoma and the expression of related factors

背景:目前国内已有较多采用利妥昔单抗联合自体外周血干细胞移植治疗弥漫大B细胞淋巴瘤的临床报道,但其作用机制还不是很明确。目的:对比分析利妥昔单抗联合自体外周血干细胞移植与利妥昔单抗治疗弥漫大B细胞淋巴瘤的效果与相关因子水平的变化。方法:选择96例弥漫大B细胞淋巴瘤患者为研究对象,其中男62例,女34例,年龄20-75岁。48例采用利妥昔单抗联合化疗方案(对照组),另48例采用利妥昔单抗联合化疗、自体外周血造血干细胞移植方案(试验组),对比两组临床疗效、不良反应发生情况,随访记录患者生存期,治疗前、化疗6个疗程后及移植后6个月,检测两组血清血管内皮生长因子、碱性成纤维细胞生长因子及白细胞介素17水平。结果与结论:①试验组患者均采集到了足够的外周血造血干细胞,回输CD34+细胞数为(3.6±0.6)×106/kg,回输后中性粒细胞植入时间为(11.1±1.2)d,血小板植入时间为(12.3±2.4)d;②试验组治疗有效率明显高于对照组(81%,56%,P<0.05);③从确诊开始至随访结束,试验组生存率为79%、无进展生存率为50%,对照组生存率为56%、无进展生存率为31%,两组间生存率与无病生存率比较差异显著(P<0.05);④两组不良反应发生情况比较差异无显著性意义(P>0.05);⑤治疗前与化疗6个疗程后,两组间3种细胞因子水平比较差异无显著性意义;与治疗前比较,两组化疗6个疗程后的白细胞介素17水平升高(P<0.05),血管内皮生长因子、碱性成纤维细胞生长因子水平降低(P<0.05);与化疗6个疗程后比较,试验组移植后6个月的白细胞介素17水平升高(P<0.05)、血管内皮生长因子、碱性成纤维细胞生长因子水平降低(P<0.05),对照组3种细胞因子水平无显著变化(P<0.05);⑥结果表明,利妥昔单抗联合自体外周血干细胞移植可提高弥漫大B细胞淋巴瘤患者的生存期,其作用途径可能与调控白细胞介素17、血管内皮生长因子、碱性成纤维细胞生长因子水平有关。

BACKGROUND:At present,there are many clinical reports of rituximab combined with autologous peripheral blood stem cell transplantation in the treatment of diffuse large B-cell lymphoma,but its mechanism is not very clear.OBJECTIVE:To compare and analyze the effects of rituximab combined with autologous peripheral blood stem cell transplantation and rituximab in the treatment of diffuse large B-cell lymphoma and changes in the levels of related factors.METHODS:96 patients with diffuse large B-cell lymphoma were selected,including 62 males and 34 females,aged 20-75 years.Among them,48 cases were treated with rituximab combined chemotherapy(control group),and the other 48 cases were treated with rituximab combined chemotherapy and autologous peripheral blood hematopoietic stem cell transplantation(trial group).The clinical efficacy and adverse reactions of the two groups were compared.The survival time of the patients was followed up and recorded.Before treatment,after 6 cycles of chemotherapy and 6 months after transplantation,the serum vascular endothelial growth factor and basic fibroblast growth factor and interleukin-17 levels were detected in both groups.RESULTS AND CONCLUSION:(1)Adequate peripheral blood hematopoietic stem cells were collected in the experimental group.The number of CD34+cells transfused back was(3.6±0.6)×10^(6)/kg.After transfusion,the time of neutrophil implantation was(11.1±1.2)days,and the time of platelet implantation was(12.3±2.4)days.(2)The effective rate of treatment in the experimental group was significantly higher than that in the control group(81%,56%,P<0.05).(3)From the beginning of definite diagnosis to the end of follow-up,the survival rate was 79%and the progression-free survival rate was 50%in the trial group.The survival rate was 56%and the progression-free survival rate was 31%in the control group.The difference in survival rate and progression-free survival rate between the two groups was significant(P<0.05).(4)There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).(5)There was no significant difference in the levels of three kinds of cytokines between the two groups before treatment and after 6 cycles of chemotherapy.Compared with before treatment,the levels of interleukin-17 increased(P<0.05),and the levels of vascular endothelial growth factor and basic fibroblast growth factor decreased after 6 cycles of chemotherapy(P<0.05).Compared with that after 6 cycles of chemotherapy,the level of interleukin-17 in the trial group increased 6 months after transplantation(P<0.05),and the levels of vascular endothelial growth factor and basic fibroblast growth factor decreased(P<0.05),and there was no significant change in the levels of three kinds of cytokines in the control group(P<0.05).(6)It is concluded that rituximab combined with autologous peripheral blood stem cell transplantation can improve the survival of patients with diffuse large B-cell lymphoma,and its mechanism may be related to the regulation of interleukin 17,vascular endothelial growth factor and basic fibroblast growth factor levels.