CD19靶向CAR T细胞于亲缘半相合干细胞移植前后2次挽救治疗复发Ph+B-ALL 1例并文献复习  

Anti-CD19-CAR T-cell in salvage therapy of relapsed B-ALL patient before and after haplo-HSCT:a successful case and analysis

作　　者：余先球[1] 费小明[1] 王丽霞[1] 雷芳[1] 陆雯萍 曹江 汤郁[2] YU Xianqiu;FEI Xiaoming;WANG Lixia;LEI Fang;LU Wenping;CAO Jiang;TANG Yu(Department of Hematology,Affiliated Hospital of Jiangsu University,Zhenjiang,Jiangsu 212001,China)

机构地区：[1]江苏大学附属医院血液科,江苏镇江212001 [2]江苏大学附属医院风湿免疫科,江苏镇江212001 [3]徐州医科大学附属医院血液科,江苏徐州221004

出　　处：《淮海医药》2022年第2期133-136,共4页Journal of Huaihai Medicine

基　　金：江苏省社会发展重点项目(临床前沿技术)课题(BE2020681);江苏省卫生健康委科研课题(H2018084)。

摘　　要：目的:报道1例费城染色体阳性B细胞急性淋巴细胞白血病(Ph+B-ALL)患者在接受亲缘半相合造血干细胞移植前后接受同一构建的CD19靶向嵌合抗原受体T细胞(CAR T)挽救治疗的结果和经验。方法:1例Ph+B-ALL患者常规化疗后第1次复发,接受自体CD19靶向CAR T细胞治疗后获分子生物学缓解并桥接亲缘半相合异基因造血干细胞移植治疗,移植1年后再复发,采用患者来源淋巴细胞再次制备同一构建的CD19靶向CAR T细胞再次挽救治疗。结果:第1次血液学复发后经自体CD19靶向CAR T细胞挽救治疗获完全获解,此后桥接亲缘半相合异基因造血干细胞移植,供者细胞在患者体内植入并完全嵌合。移植后患者接受达沙替尼维持治疗。移植1年后患者再次血液学复发,嵌合度STR 88.7%,ABL激酶区未检测出已知突变。单采患者体内淋巴细胞,制备同一构建的CD19靶向CAR T细胞。患者经第2次CAR T细胞挽救治疗后再获分子生物学缓解。患者第1次CAR T细胞治疗中未发生细胞因子释放综合征(CRS)等不良事件,第2次CAR T细胞治疗后出现I度CRS,无GVHD。目前该患者正在接受供者淋巴细胞输注治疗。结论:对于移植前接受过CD19靶向CAR T细胞治疗的Ph+B-ALL,移植后复发时再次接受同一构建的CD19靶向CAR T细胞治疗仍然有效;对于半相合移植后复发患者,采用患者来源的淋巴细胞制备CAR T细胞进行挽救治疗,是一个可行且安全的挽救治疗方法。Objective:To report a salvage case of a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+B-ALL),who received chimeric antigen receptor T-cell(CAR T-cell)therapy before and after haplo-HSCT.Methods:A patient with Ph+B-ALL relapsed after conventional chemotherapy.After receiving autologous CD19-CAR T-cell therapy,the patient gained molecular biology remission followed by allogeneic hematopoietic stem cell transplantation.One year after,the patient relapsed again.The salvage therapy was for the second time conducted,using the same CD19-target CAR T-cell construct from the patient's own lymphocytes.Results:After the first hematological relapse,the patient got complete remission with the CD19-target CAR T-cell salvage therapy,which was followed by haplo-HSCT.Cells from the donor were transplanted into the patient and complete chimerism was achieved.After the transplantation,the patient received maintenance treatment with dasatinib.One year after the transplant,hematological relapse occurred again,with STR 88.7%.The known mutation was not detected in ABL kinase domain.The patient underwent lymphocyte apheresis and the same CD19-target CAR T-cell construct was prepared.The patient regained molecular biology remission after the second CAR T-cell salvage therapy.Adverse reaction such as cytokine release syndrome(CRS)did not occur in the first CAR T-cell therapy.Grade I CRS and no GVHD were found in the second CAR T-cell therapy.At present,the patient is receiving the donor lymphocyte infusion.Conclusion:For the Ph+B-ALL who received CD19-target CAR T-cell therapy before transplantation,the therapy remains effective when relapse occurs after the transplantation.For patients who relapse after haplo-HSCT,it is a feasible and safe salvage therapy to prepare CAR T cells by receiving lymphocytes from the patient.

关 键 词：急性淋巴细胞白血病 费城染色体 嵌合抗原受体T细胞 半相合造血干细胞移植 

分 类 号：R733.71[医药卫生—肿瘤]