摘要
目的观察嵌合抗原受体(CAR)-T细胞免疫治疗桥接异基因造血干细胞移植(allo-HSCT)患者的免疫重建表现。方法回顾性分析2018年8月至2021年12月期间在北京陆道培医院接受CAR-T细胞桥接allo-HSCT治疗的所有急性B淋巴细胞白血病(B-ALL)患者临床病历资料,年龄14(7,30)岁,其中男39例,女22例。CAR-T细胞免疫治疗32例,非CAR-T细胞免疫治疗29例。随访时间561(235,784)d。用多色流式检测患者移植前及移植后1、2、3、6、8、10、12个月外周血各淋巴细胞亚群即总淋巴细胞、T淋巴细胞、辅助性T细胞、细胞毒性T细胞、B淋巴细胞、自然杀伤细胞、Treg细胞计数,以评估患者在移植后免疫重建表现。结果移植前血清球蛋白:CAR-T组IgA水平0.18(0.06,0.49)g/L低于非CAR-T组1.03(0.63,1.56)g/L患者(U=103.5,P<0.001)。CAR-T组IgG水平5.54(4.04,7.09)g/L低于非CAR-T组6.78(5.27,9.26)g/L(U=1298.5,P=0.017),CAR-T组IgM水平0.18(0.05,0.30)g/L低于非CAR-T组0.40(0.26,0.71)g/L(U=166.0,P<0.001)。CAR-T组移植前外周血免疫细胞总淋巴细胞计数833.00(335.00,1727.50)个/μl,低于非CAR-T组患者1052.00(545.75,1812.50)个/μl(U=404.0,P<0.001)。移植前CAR-T组T淋巴细胞绝对计数686.00(233.00,1307.00)个/μl,低于非CAR-T组患者860.00(391.00,1419.75)个/μl(U=406.0,P<0.001)。CAR-T组辅助性T淋巴细胞绝对计数146.00(40.50,327.50)个/μl,低于非CAR-T组患者162.50(66.00,384.75)个/μl,(U=494.0,P=0.002)。CAR-T组细胞毒性T淋巴细胞绝对计数343.00(56.50,924.00)个/μl,低于非CAR-T组患者478.00(143.50,992.25)个/μl(U=483.5,P=0.001)。CAR-T组B淋巴细胞绝对计数22.00(6.00,186.00)个/μl,低于非CAR-T组患者33.00(8.00,220.00)个/μl(U=498.0,P=0.002)。而2组患者移植后监测时间点上述各免疫细胞亚群细胞绝对计数差异均无统计学意义(P>0.05)。对比2组患者临床特征,CAR-T组患者移植前病史981.00(368.50,1514.75)d比非CAR-T组323.00(167.50,450.50)d长(U=263.0,P=0.004),CAR-T组患者预处理方案中兔抗人胸腺细胞免疫球蛋白(ATG)用量5.00(5.00,7.50)mg/kg比非CAR-T组患者7.00(5.00,7.50)mg/kg低(U=288.5,P=0.018),CAR-T组移植物CD34+回输剂量5.91(4.23,6.02)×10^(6)/kg比非CAR-T组患者高4.51(4.00,5.93)×10^(6)/kg(U=291.0,P=0.012),CAR-T组移植后环孢素应用时间167.00(119.25,299.50)d,比非CAR-T组患者197.00(102.50,450.50)d短(U=421.0,P=0.001)。结论对于移植前免疫功能偏低的CAR-T患者,可通过降低预处理ATG剂量、增加移植物CD34+输注剂量、移植后尽早停用环孢素等方式,使其与非CAR-T患者达到相似的免疫重建状态。
Objective To study the performance of immune reconstitution in patients with chimeric antigen receptor(CAR)-T cell immunotherapy bridging allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods A total of 61 patients with acute B lymphocytic leukemia(B-ALL)who received CAR-T cell bridging allo-HSCT in Beijing Lu Daopei Hospital from August 2018 to December 2021 were enrolled,and the clinical medical records of the above patients were retrospectively analyzed.The average age was 14(7,30)years old,including 39 males and 22 females.32 patients were treated with CAR-T cell immunotherapy(CAR-T Group)and 29 didn't with CAR-T cell immunotherapy(non-CAR-T group).The follow-up period was 561(235,784)days.Multicolor flow cytometry was used to detect the peripheral blood lymphocyte subsets,i.e.total lymphocytes,T lymphocytes,helper T cells,cytotoxic T cells,B lymphocytes,NK cells,and Treg cell counts before transplantation and 1,2,3,6,8,10,and 12 months after transplantation,to evaluate the immune reconstitution performance post allo-HSCT.Results Serum globulin before transplantation:The IgA level in the CAR-T group was 0.18(0.06,0.49)g/L,which was lower than that of 1.03(0.63,1.56)g/L in the non-CAR-T group(U=103.5,P<0.001).The IgG level in the CAR-T group was 5.54(4.04,7.09)g/L,lower than that of 6.78(5.27,9.26)g/L in the non-CAR-T group,(U=1298.5,P=0.017),and the IgM level in the CAR-T group was 0.18(0.05,0.30)g/L,lower than that of 0.40(0.26,0.71)g/L in the non-CAR-T group(U=166.0,P<0.001).In the CAR-T group before transplantation,the absolute count of total lymphocyte in peripheral blood was 833.00(335.00,1727.50)/μl,lower than that of 1052.00(545.75,1812.50)/μl in the non-CAR-T group(U=404.0,P<0.001).The absolute count of T lymphocyte in the CAR-T group before transplantation was 686.00(233.00,1307.00)/μl,lower than that of 860.00(391.00,1419.75)/μl in the non-CAR-T group(U=406.0,P<0.001).The absolute count of helper T lymphocytes in the CAR-T group was 146.00(40.50,327.50)/μl,lower than that of 162.50(66.00,384.75)/μl in the non-CAR-T group(U=494.0,P=0.002).The absolute count of cytotoxic T lymphocytes in the CAR-T group was 343.00(56.50,924.00)/μl,lower than that of 478.00(143.50,992.25)/μl in the non-CAR-T group(U=483.5,P=0.001).The absolute count of B lymphocytes in CAR-T group was 22.00(6.00,186.00)/μl,lower than that of 33.00(8.00,220.00)/μl in the non-CAR-T group(U=498.0,P=0.002).And when two groups of patients were monitored after transplantation,there was no statistical difference in absolute cell counts of each immune cell subpopulation(P>0.05).Comparing the clinical features of the two groups,the pre-transplant history of the CAR-T group was 981.00(368.50,1514.75)d,longer than that of 323.00(167.50,450.50)d in the non-CAR-T group(U=263.0,P=0.004).The dose of rabbit anti-human thymic immunoglobulin(ATG)in the pretreatment protocol of patients in the CAR-T group was 5.00(5.00,7.50)mg/Kg,lower than that of 7.00(5.00,7.50)mg/kg in the non-CAR-T group(U=288.5,P=0.018).The infusion dose of CD34+cells in the CAR-T group was 5.91(4.23,6.02)×10^(6)/kg,higher than that of 4.51(4.00,5.93)×10^(6)/kg in the non-CAR-T group(U=291.0,P=0.012).The duration of the application of cyclosporine after transplantation in the CAR-T group was 167.00(119.25,299.50)d,which was shorter than that of 197.00(102.50,450.50)d in the non-CAR-T group(U=421.0,P=0.001).Conclusions For patients in CAR-T group with low immune function before transplantation,it may be possible to make them comparable to non-CAR-T group in immune reconstitution state by reducing the dose of pretreatment ATG,increasing the counts of CD34+cells infusion in the graft,and discontinuing cyclosporine as soon as possible after transplantation.
作者
赵玮
陈曼
胡培娟
陈美花
安彦彦
王卉
赵艳丽
Zhao Wei;Chen Man;Hu Peijuan;Chen Meihua;An Yanyan;Wang Hui;Zhao Yanli(Department of Transplantation,Beijing Lu Daopei Hospital,Beijing 100176,China;Laboratory Department,Hebei Yanda Lu Daopei Hospital,Langfang 065201,China;Department of Transplantation,Hebei Yanda Lu Daopei Hospital,Langfang 065201,China)
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2022年第8期833-839,共7页
Chinese Journal of Laboratory Medicine
关键词
造血干细胞移植
CAR-T治疗
免疫细胞亚群
免疫重建
Hematopoietic stem cell transplantation
CAR-T cell immunotheropy
Immune cell subsets
Immune reconstitution
