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序贯抗 CD19、22 和 20 自体嵌合抗原受体 T 细胞(CAR-T)治疗复发难治性伯基特淋巴瘤患儿:病例报告及文献复习。

Sequential anti-CD19, 22, and 20 autologous chimeric antigen receptor T-cell (CAR-T) treatments of a child with relapsed refractory Burkitt lymphoma: a case report and literature review.

机构信息

Tianjin Medical University, Tianjin, 300070, China.

Children's Lymphoma Ward, Beijing Boren Hospital, Beijing, 100070, China.

出版信息

J Cancer Res Clin Oncol. 2020 Jun;146(6):1575-1582. doi: 10.1007/s00432-020-03198-7. Epub 2020 Mar 28.

Abstract

PURPOSE

Burkitt lymphoma (BL) is one of the most frequent subtypes of non-Hodgkin lymphoma (NHL) in children. Currently, short, intensive chemotherapy is used internationally and has greatly improved survival in children with BL. However, 5-10% of patients suffer recurrence after intensive chemotherapy, and the prognosis of these patients remains poor. The overall survival rate is only approximately 10%. Innovative therapies are needed to attain a higher rate of remission, such as immunotherapy for relapsed refractory (r/r) BL patients.

METHODS

An 8-year-old boy with BL was studied. He suffered a relapse after treatment with standard chemotherapy. Then, we treated this patient using autologous chimeric antigen receptor T-cell (CAR-T) therapies, sequentially targeting antigens CD19, CD22, and CD20. A review of the current literature on CAR-T treatment for lymphoma is presented.

RESULTS

The patient had no discernible response to anti-CD19 CAR-T treatment and exhibited progressive disease (PD). Following CD-22-directed CAR-T treatment, the patient underwent a partial remission (PR), but unfortunately a relapse rapidly occurred. Finally, after administering the anti-CD20 CAR-T cell therapy, the child went into complete remission (CR). The young boy has currently achieved 16-month event-free survival (EFS) so far. During administration of the CD19 and CD20 CAR-T cells, the patient appeared to experience mild (Grade I) cytokine release syndrome (CRS). However, during the CD22 CAR-T therapy, he appeared to experience grade III CRS.

CONCLUSION

Autologous anti-CD19, anti-CD22, and anti-CD20 CAR-T cell therapies targeting multiple tumor antigens could be an innovative and sound treatment for children with r/r BL, provided that they are closely monitored during treatment.

摘要

目的

伯基特淋巴瘤(BL)是儿童中最常见的非霍奇金淋巴瘤(NHL)亚型之一。目前,国际上采用短期强化化疗,大大提高了 BL 患儿的生存率。然而,5-10%的患者在强化化疗后复发,这些患者的预后仍然较差。总生存率仅约为 10%。需要创新疗法来提高缓解率,例如针对复发难治(r/r)BL 患者的免疫疗法。

方法

研究了一名 8 岁 BL 男孩。他在标准化疗后复发。然后,我们使用自体嵌合抗原受体 T 细胞(CAR-T)疗法对该患者进行治疗,依次靶向抗原 CD19、CD22 和 CD20。介绍了针对淋巴瘤的 CAR-T 治疗的当前文献综述。

结果

该患者对抗 CD19 CAR-T 治疗无明显反应,表现为疾病进展(PD)。在 CD-22 定向 CAR-T 治疗后,患者出现部分缓解(PR),但不幸的是,病情迅速复发。最后,在给予抗 CD20 CAR-T 细胞治疗后,患儿完全缓解(CR)。目前,这名小男孩已经达到 16 个月的无事件生存(EFS)。在给予 CD19 和 CD20 CAR-T 细胞时,患者似乎出现轻度(I 级)细胞因子释放综合征(CRS)。然而,在 CD22 CAR-T 治疗期间,他似乎出现了 III 级 CRS。

结论

针对多个肿瘤抗原的自体抗 CD19、抗 CD22 和抗 CD20 CAR-T 细胞疗法可能是 r/r BL 儿童的一种创新且合理的治疗方法,但在治疗过程中需要密切监测。

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