PMC9581047_01
Flow chart of the disease process and therapeutic modalities.
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However, the first relapse occurred 4 months after the last chemotherapy (  Figure 1  ). Approximately 2 months later, the patient disease relapsed for the second time ( Figure 1 ). Approximately 18 months after CD19 CAR-T cell treatment, no recurrence of symptoms was noted as stringent CR according to our follow-up ( Figure 1 ).
(A) The pathological section of mediastinum lymphatic tissue (upper panel: hematoxylin and eosin stain; lower panel: immunohistochemistry, CD30 negative). (B) Positron emission tomography assessment of patient first diagnosed (left) and after CAR-T cells infusion (right). The white arrow indicates the invasion of DLBCL on the mediastinum, which is the primary site. (C) Brain MRI images before and after CAR-T cell therapy. (a) Brain MRI on March 2020, after the second cycle of chemotherapy of R2-ICE*5 and evaluated as CR2. (b) Brain MRI on May 2020, when the patient showed CNS relapse. The size of the right temporal lobe and occipital lobe masses are 3.19 cmx4.03 cm and1.75 cmx2.4 cm, respectively. (c) The same region on October 2020, more than 4 months after CAR-T cells infusion. The mass almost disappeared and was evaluated as CR for 2 months. (d) The follow-up image on December 2020 with continuous CR.
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A right temporal lobe mass IHC revealed CD3-, CD20+, CD19+, CD21-, CD30-, KI-67(80%+), CD10+, C-MYC(2%), BCL-2+, BCL-6+, MUM1+, CD38-, CD5-, and CyclinD1- ( Figure 2A ) and negative EBER by FISH test. Two months later, the patient was evaluated as CR by PET/CT; brain MRI; and neck, chest, and abdomen CT scan with significant clinical response ( Figures 2B, C ).
CAR19 DNA copies, CART cell expansion levels detected by flow cytometry and the proportion of CAR-T cell to CD3+ cell during treatment. The peak levels appeared on day 14 after CAR-T cell infusion, indicating CAR19 DNA copies were 2.79x103 copies/mug, CAR-T cells expansion detected by flow cytometry was 3.64x107/L and CD3+CAR19+/CD3+ T-cell was 8.55%.
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Meanwhile, the patient's DNA copy level of the CD19 CAR-T cells in peripheral blood did not show obvious expansion, presenting as 4.6x101 copies/mug on day 4 and 5.65x101 copies/mug on day 7 ( Figure 3 ).