Liang Zuyu, Zhang Hao, Shao Mi, Cui Qu, Wu Zhao, Xiao Lei, Huang He, Hu Yongxian
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine.
Hematology Institution, Zhejiang University, Hangzhou.
Medicine (Baltimore). 2020 Oct 23;99(43):e22510. doi: 10.1097/MD.0000000000022510.
Chimeric antigen receptor T cells (CAR-T) targeting CD19 have shown great potential for treatment of B-cell malignancies. For those patients who can not achieve complete remission (CR) or suffer from relapse after CAR-T therapy, further therapeutic strategies still remain elusive. Whether existing CAR-T cells can revitalize in vivo and eradicate tumor cells is still unknown.
We report a case of diffused large B-cell lymphoma patient who had achieved CR after CD19 targeted CAR-T therapy but relapsed after 5 months.
Five months after CAR-T cell infusion, the patient was confirmed a relapse by follow-up PET/CT scan and a mass biopsy. Flow cytometry showed a dramatically decreased percentage of CAR-T cells in peripheral blood (PB).
A second anti-CD19 CAR-T therapy was planned with deliberation. Firstly, the patient received lymphodepletion chemotherapy with fludarabine (25 mg/m, d1-d3) and cyclophosphamide (500 mg/m d2-d3).
After fludarabine and cyclophosphamide (FC) lymphodepletion chemotherapy, pre-existing CAR-T cells were revitalized and the patient developed grade 2 cytokine release syndrome (CRS) contributing to the regression of relapsed B-cell lymphoma.
This case suggested that FC chemotherapy could revitalize CAR-T cells contributing to the regression of relapsed B-cell lymphoma. Nevertheless, further researches are required in the future as this report described only a single case.
靶向CD19的嵌合抗原受体T细胞（CAR-T）在治疗B细胞恶性肿瘤方面显示出巨大潜力。对于那些无法实现完全缓解（CR）或在CAR-T治疗后复发的患者，进一步的治疗策略仍然难以捉摸。现有的CAR-T细胞能否在体内恢复活力并根除肿瘤细胞仍不清楚。
我们报告了1例弥漫性大B细胞淋巴瘤患者，该患者在接受靶向CD19的CAR-T治疗后达到CR，但5个月后复发。
CAR-T细胞输注5个月后，通过后续PET/CT扫描和肿块活检证实患者复发。流式细胞术显示外周血（PB）中CAR-T细胞百分比显著下降。
慎重计划进行第二次抗CD19 CAR-T治疗。首先，患者接受了氟达拉滨（25mg/m²，第1 - 3天）和环磷酰胺（500mg/m²，第2 - 3天）的淋巴细胞清除化疗。
氟达拉滨和环磷酰胺（FC）淋巴细胞清除化疗后，先前存在的CAR-T细胞恢复活力，患者出现2级细胞因子释放综合征（CRS），这有助于复发的B细胞淋巴瘤消退。
该病例表明FC化疗可使CAR-T细胞恢复活力，有助于复发的B细胞淋巴瘤消退。然而，由于本报告仅描述了1例病例，未来仍需要进一步研究。
