自体造血干细胞移植序贯靶向CD19和CD22嵌合抗原受体T细胞治疗肾弥漫大B细胞淋巴瘤中枢神经系统复发1例并文献复习

Sequential therapy of targeting CD19 and CD22 chimeric antigen receptor T⁃cell following autologous stem cell transplantation for renal diffuse large B⁃cell lymphoma with central nervous system recurrence:report of 1 case and review of literature

目的探讨自体造血干细胞移植(ASCT)序贯靶向CD19和CD22嵌合抗原受体T细胞(CAR-T)治疗肾弥漫大B细胞淋巴瘤(DLBCL)中枢神经系统复发的效果及安全性。方法回顾性分析华中科技大学同济医学院附属同济医院2019年5月收治的1例肾DLBCL中枢神经系统复发患者的临床资料。患者应用ASCT序贯靶向CD19和CD22 CAR-T治疗,分析治疗后1、3、6、12、18、24个月原发病缓解相关指标,并复习相关文献。结果患者,男性,23岁,R-CHOP方案治疗8个疗程后中枢神经系统复发,应用ASCT序贯靶向CD19和CD22 CAR-T治疗。患者发生1级细胞因子释放综合征,经积极治疗后病情稳定。患者白细胞、血小板成功植入,中枢神经系统症状完全消失,脑脊液检查示幼稚细胞消失。应用液体活组织检查动态追踪微小残留病,患者持续缓解26个月。移植后1年发现肺结核,经过抗结核治疗后痊愈。结论ASCT序贯靶向CD19和CD22 CAR-T疗法为肾DLBCL继发中枢神经系统侵犯的患者提供了新的治疗手段,尤其对于常规化疗或单用CAR-T疗效不佳的患者,该方案可能有效提高治疗缓解率,改善生存。

Objective To investigate the efficacy and safety of sequential therapy of targeting CD19 and CD22 chimeric antigen receptor T-cell(CAR-T)following autologous stem cell transplantation(ASCT)in treatment of renal diffuse large B-cell lymphoma(DLBCL)with central nervous system(CNS)recurrence.Methods The clinical data of 1 renal DLBCL patient with CNS recurrence admitted to Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology in May 2019 were retrospectively analyzed.The patient received sequential therapy of targeting CD19 and CD22 CAR-T following ASCT.The relative indicators of the primary disease remission at 1,3,6,12,18 and 24 months after therapy were recurrence after 8 courses of R-CHOP chemotherapy and then he received sequential therapy of targeting CD19 and CD22 CAR-T following ASCT.During the process of treatment,this patient developed grade 1 cytokine release syndrome and his condition was well controlled after active treatment.The white blood cell and platetes were successfully implanted.CNS symptoms along with immature cells in cerebrospinal fluid disappeared completely.Liquid biopsy was used to dynamically monitor the residue disease of the patient and the duration of remission period lasted 26 months.This patient developed tuberculosis one year after treatment and recovered from anti-tuberculosis agents.Conclusions Sequential therapy of targeting CD19 and CD22 CAR-T following ASCT provides a novel therapeutic approach for renal DLBCL with CNS recurrence.Especially for patients who are neither sensitive to conventional chemotherapy nor CAR-T therapy alone,this regimen may improve remission rate and survival.