成功救治2例CAR-T细胞治疗后伴严重细胞因子风暴和相关性脑病伴文献复习  

Successful Treatment of Cytokine Release Syndrome and CAR-T Cell-related Encephalopathy Syndrome:A Report of Two Cases and Literature Review

作　　者：强萍 薛磊 汪敏 许汉英 刘欣[1] 朱薇波 杨林 王兴兵 QIANG Ping;XUE Lei;WANG Min(The First Affiliated Hospital of University of Science and Technology of China,Hefei 230000)

机构地区：[1]中国科学技术大学附属第一医院(安徽省立医院)血液内科,合肥230001 [2]博生吉安科细胞技术有限公司

出　　处：《临床输血与检验》2020年第4期413-419,共7页Journal of Clinical Transfusion and Laboratory Medicine

基　　金：安徽省科技计划项目(No.1604a0802071)资助。

摘　　要：目的探讨CAR-T相关性脑病综合征(CRES)和细胞因子释放综合征(CRS)的临床诊治。方法复习2例CAR-T细胞治疗后伴严重细胞因子风暴和相关性脑病患者临床资料及治疗经过,并结合文献复习。结果2例患者均表现为癫痫、发热、血压下降、低氧血症、窦性心动过速及凝血功能异常。CRP、血清铁蛋白(SF)、白细胞介素(IL)-2、IL-6和IL-10均明显升高。诊断为CRS(3级)和CRES(3级)。CRS发病时间为CAR-T细胞输注后第2 d和第7 d,而CRES发病时间为第4 d和第10 d。第1例患者使用托珠单抗(8 mg/kg)联合DXM(20 mg/d)治疗,临床症状迅速缓解。第2例患者出现CRS加用托珠单抗(8 mg/kg)及DXM(20 mg/d)治疗后,仍发生CRES,改为甲强龙(1 g/d),临床症状缓解。结论密切监测CAR-T细胞治疗后的不良反应,及时有效地处理CRS和CRES,有助于提高CAR-T细胞治疗的安全性。Objective To further study the diagnosis and treatment of CAR-T cell-related encephalopathy syndrome(CRES)and cytokine release syndrome(CRS),we reviewed two cases of CRES and CRS retrospectively.Methods Clinic data of two patients with relapsed or refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL)after treated by CAR-T cell immunotherapy were analyzed combined with review of literature.Results Both of the two patients developed severe CRS(Grade 3)and CRES(Grade 3).They were both developed epilepsy,hyperpyrexia,hypotension,hypoxia,tachycardia,and coagulation disorders.The level of C-reactive protein(CRP),Serum ferritin(SF),Interleukin(IL)-2,IL-6 and IL-10 were significant increased.The timing of onset for CRS were the 2th or 7th day after CAR-T cell transfusion,while CRES were 4th or 10th day,respectively.The first patient was treated with tocilizumab(8 mg/kg)and dexamethasone(20 mg/d),then clinical symptoms were obviously alleviated.The second patient was treated with tocilizumab(8 mg/kg)and dexamethasone(20mg/d),but still developed CRES,so switch to methylprednisolone(1 g/d),then the clinical symptoms were obviously alleviated.All of the two patients appeared to make a full recovery.Conclusion Monitoring of toxicities after CAR-T cell therapy and quick management of CRS and CRES are helpful for improvement of a clinical efficacy and safety in the treatment of CRES for patients with R/R B-ALL treated by CAR-T cell immunotherapy.

关 键 词：嵌合抗原受体修饰T细胞 托珠单抗 细胞因子释放综合征 CAR-T相关性脑病综合征 急性淋巴细胞白血病 

分 类 号：R730.51[医药卫生—肿瘤]