目的 探讨嵌合抗原受体T细胞(CAR-T)免疫疗法对复发/难治性弥漫大B细胞淋巴瘤(DLBCL)患者乳酸脱氢酶(LDH)、淋巴细胞绝对值(ALC)、CD4+/CD8+、肿瘤增殖抗原(Ki67)表达的影响.方法 回顾性选取复发/难治性DLBCL患者92例,均经CAR-T细胞免疫治疗.记录复发/难治性DLBCL患者临床疗效及不良反应,比较治疗前后复发/难治性DLBCL患者LDH、ALC、CD4+/CD8+、Ki67水平.观察不同疗效患者治疗前临床特征,包括性别、年龄、AnnArbor分期、ECOG评分、结外受累部位、国际预后指数(IPI)、CAR-T治疗线数,以及治疗前LDH、ALC、CD4+/CD8+、Ki67 水平.结果 CAR-T 免疫治疗后 CR 39 例(42.39%),PR 24 例(26.09%),SD 18 例(19.57%),PD 11 例(11.96%);总有效63例(68.48%).不良反应细胞因子释放综合征(CRS)71例(77.17%),低免疫球蛋白血症73例(79.35%).经CAR-T细胞免疫治疗后LDH、Ki67水平较治疗前下降,ALC、CD4+/CD8+较治疗前上升,差异具有统计学意义(P<0.05).DLBCL治疗无效患者年龄、AnnArbor分期、结外受累部位数量、IPI、LDH、Ki67、CAR-T治疗线数均高于治疗有效组患者,ALC、CD4+/CD8+均低于治疗有效组患者(P<0.05).Logistic回归分析显示高龄、AnnArborⅣ期、多结外受累部位数量、高IPI得分、二线以上CAR-T以及治疗前LDH、Ki67的水平升高和ALC、CD4+/CD8+的水平降低是影响DLBCL患者CAR-T细胞免疫治疗疗效的危险因素(P<0.05).建立ROC曲线,LDH、ALC、CD4+/CD8+、Ki67 AUC分别为0.823、0.835、0.873、0.849,提示LDH、ALC、CD4+/CD8+、Ki67对CAR-T细胞免疫治疗疗效具有一定的预测价值.结论 CAR-T细胞免疫疗法可降低LDH、Ki67水平表达,升高ALC和CD4+/CD8+表达,且治疗前LDH、ALC、CD4+/CD8+、Ki67表达对CAR-T细胞免疫疗法疗效具有预测价值.
Objective To investigate the effects of chimeric antigen receptor T cell(car-t)immunotherapy on lactate dehydrogenase(LDH),absolute lymphocyte count(ALC),CD4+/CD8+ratio,and tumor proliferating antigen(Ki67)expres-sion in patients with relapsed/refractory diffuse large B cell lymphoma(DLBCL).Methods A total of 92 patients with relapsed/refractory DLBCL who were definitely diagnosed by car-t cell immunotherapy were retrospectively analyzed.Clinical outcomes and adverse effects were recorded in patients with relapsed/refractory DLBCL,and the levels of LDH,ALC,CD4+/CD8+ratio,and Ki67 were compared between patients with relapsed/refractory DLBCL before and after treatment.Pretreatment clinical character-istics,including gender,age,annarbor stage,ECoG score,site of extranodal involvement,international prognostic index(IPI),number of lines of car-t therapy,and pretreatment LDH,ALC,CD4+/CD8+ratio,and Ki67 levels,were evaluated in patients with different efficacies.Results After car-t immunotherapy,39 patients(42.39%)had Cr,24 patients(26.09%)had pr,18 patients(19.57%)had SD,and 11 patients(11.96%)had PD;The overall response rate was 63 patients(68.48%).71 pa-tients(77.17%)had adverse reaction cytokine release syndrome(CRS)and 73 patients(79.35%)had hypoimmunoglobuline-mia.LDH and Ki67 levels decreased and ALC and CD4+/CD8+ratio increased after car-t cell immunotherapy compared with those before treatment,respectively(P<0.05).The age,annarbor stage,the number of extranodal involved sites,the number of IPI,LDH,Ki67 and car-t treatment lines of patients with DLBCL who failed to respond to treatment were higher than those in the effective treatment group,and the ALC and CD4+/CD8+ratios were lower than those in the effective treatment group(P<0.05).Logistic regression analysis showed that advanced age,annarbor stage IV,number of sites with multiple extranodal involve-ment,high IPI score,car-t beyond second-line as well as increased levels of pretreatment LDH,Ki67 and decreased levels of ALC,CD4+/CD8+ratio were risk factors affecting the efficacy of car-t cell immunotherapy in DLBCL patients(P<0.05).ROC curves were established,and the AUCs of LDH,ALC,CD4+/CD8+ratio,and Ki67 were 0.823,0.835,0.873,and 0.849,re-spectively,suggesting that LDH,ALC,CD4+/CD8+ratio,and Ki67 may have some predictive value for the efficacy of car-t cell immunotherapy.Conclusion car-t cell immunotherapy reduced LDH and Ki67 level expression and increased ALC and CD4+/CD8+ratio expression,and pretreatment LDH,ALC,CD4+/CD8+ratio,and Ki67 expression were predictive of car-t cell immu-notherapy efficacy.