复发难治型急性淋巴细胞白血病患者CAR-T细胞治疗后外周血Foxp3n +Tregs水平在其临床疗效评估中的价值研究n

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目的:探讨复发难治型急性淋巴细胞白血病(relapsed refractory acute lymphoblastic leukemia, R/R ALL)患者行嵌合抗原受体T细胞(chimeric antigen receptor T-Cell,CAR-T)免疫疗法治疗后复发与外周血Foxp3n +调节性T细胞(regulatory T cells, Tregs)水平的关系。n 方法:选取徐州医科大学附属医院2016年1月至2019年1月R/R ALL患者43例设为研究组,另选取同期健康体检者43例设为对照组。采取CAR-T细胞免疫疗法对患者进行治疗,抽取所有研究对象空腹外周血液样本采用流式细胞术测定T淋巴细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs水平。对比分析研究组与对照组不同疗效、不同预后效果患者T细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs比例,分析各指标与疗效、预后关联性。n 结果:研究组T细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs比例分别为(67.32±13.29)%、(5.40±1.35)%、(4.81±1.28)%,明显高于对照组的(25.81±7.61)%、(3.10±0.66)%、(2.80±0.75)%,不同疗效患者T细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs间差异存在统计学意义(n P值均<0.05),部分缓解者T细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs比例分别为(46.18±10.22)%、(4.13±1.12)%、(3.64±0.91)%,未缓解者分别为(68.29±14.13)%、(5.51±1.40)%、(4.93±1.32)%,部分缓解者明显低于未缓解者,完全缓解者T细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs比例分别为(30.79±6.53)%、(3.29±0.73)%、(2.91±0.80)%,均低于部分缓解者(n P值均<0.05);无复发者T细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs分别为(29.79±7.01)%、(3.18±0.75)%、(2.86±0.79)%,复发者分别为(66.13±14.06)%、(5.33±1.30)%、(4.77±1.13)%,无复发者低于复发者(n P值均<0.05);T细胞、CD4n +CD25n +Tregs、CD4n +CD25n +Foxp3n +Tregs与临床疗效、预后呈负相关(n r=-0.661、-0.791、-0.766、-0.621、-0.761、-0.772,n P值均<0.05)。n 结论:R/R ALL患者外周血Foxp3n +Tregs水平存在异常,且经CAR-T细胞免疫疗法治疗后不同疗效、不同复发情况患者CD4n +CD25n +Foxp3n +Tregs等具有明显差异,两者间存在负相关关系。n “,”Objective:To investigate the relationship between recurrence and the level of Foxp3 n + regulatory T cells (Tregs) in peripheral blood in patients with relapsed refractory acute lymphoblastic leukemia (R/R ALL) after treatment with chimeric antigen receptor T-Cell immunotherapy (CAR-T).n Method:From January 2016 to January 2019, 43 patients with R/R ALL relapsed and refractory acute lymphoblastic leukemia in Affiliated Hospital of Xuzhou Medical University were selected as the study group, and 43 healthy people in the same period were selected as the control group. Fasting peripheral blood samples were taken after admission to the hospital to determine the ratio of T cell, CD4n + CD25n + Tregs, CD4n + CD25n + Foxp3n + Tregs using flow cytometry. and CAR-T cell immunotherapy was used.The proportion of T cell, CD4n + CD25n + Tregs, CD4n + CD25n + Foxp3n + Tregs in the study group and the control group, patients with different curative effects and different prognostic effects were counted, and the correlation between each index and curative effect and prognosis was analyzed.n Result:The proportion of T cells, CD4n + CD25n + Tregs and CD4n + CD25n + Foxp3n + Tregs in the study group were (67.32±13.29)%, (5.40±1.35)%, (4.81±1.28)%, which were significantly higher than those in the control group [(25.81±7.61)%, (3.10±0.66)%, (2.80±0.75)% ](all n P values <0.05). The percentage of T cells, CD4 n + CD25n + Tregs and CD4n + CD25n + Foxp3n + Tregs in patients with partial remission were (46.18±10.22)%, (4.13±1.12)%, (3.64±0.91)%, respectively, while those without remission were (68.29±14.13)%, (5.51±1.40)%, (4.93±1.32)%, respectively .The proportion of T cell, CD4n + CD25n + Tregs and CD4n + CD25n + Foxp3n + Tregs in complete remission group were (30.79±6.53)%, (3.29±0.73)%, and (2.91±0.80)%, respectively, which were lower than those of partial remission (all n P values <0.05) .The cell, CD4 n + CD25n + Tregs and CD4n + CD25n + Foxp3n + Tregs were (29.79±7.01)%, (3.18±0.75) and (2.86±0.79)%, respectively. The recurrence rates were (66.13±14.06)%, (5.33±1.30)%, (4.77±1.13)%, respectively. The levels of T cells, CD4n + CD25n + Tregs and CD4n + CD25n + Foxp3n + Tregs were (29.79±7.01)%, (3.18±0.75)% and (2.86±0.79)%, respectively.T Cells, CD4n + CD25n + Tregs, CD4n + CD25n + Foxp3n + Tregs were negatively correlated with clinical efficacy and prognosis (n r=-0.661, -0.791, -0.766, -0.621, -0.761, -0.772, all n P values <0.05).n Conclusion:Foxp3n + Tregs levels in peripheral blood of patients with relapsed and refractory acute lymphoblastic leukemia R/R ALL were abnormal. There were significant differences in CD4n + CD25n + Foxp3n + Tregs levels in patients with different curative effects and relapse conditions after CAR-T cell immunotherapy, and there was a significant negative correlation between them.n
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