case_images: PMC10713792_01
case_images: PET/CT images in the periods before CAR-T therapy and after CAR-T therapy. (A) Relapse after ASCT showing multiple enlarged lymph nodes with increased glucose metabolism. (B) PET/CT after combined targeted therapy showing fewer lesions with smaller volume and reduced metabolism. (C) PET/CT after CAR-T infusion showing rapid progression revealing increased lesions and metabolism. PET-CT stands for positron emission tomography-computed tomography; ASCT stands for autologous stem cell transplantation; CAR-T stands for chimeric antigen receptor T-cell.
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case_images: Unfortunately, 6 months after ASCT, the patient got PD again with new progression including multiple lymphoid enlargement of the left cervical, left subclavian, mediastinum, and abdominal cavity ( Figure 1A ). Between March and May 2022, two cycles of combined immunochemotherapy therapy (azacitidine, obinutuzumab, and mitoxantrone) were performed and the patient achieved partial remission (PR), with a small and reduced metabolism lesion left according to subsequent PET-CT ( Figure 1B ). One month after CAR-T cell infusion, PET-CT ( Figure 1C ) revealed an unexpected enlargement of multiple lymph nodes throughout the whole body, including in the bilateral clavicle area, mediastinum, right internal breast, pelvic cavity, etc., with increased metabolism.
case_images: Changes of cytokines, temperature, and hematological examinations in this relapse/refractory diffuse large B cell lymphoma patient. (A) Graph showing IL-6 and CRP changes after CAR-T infusion. (B) Graph showing temperature changes after CAR-T infusion. (C) Graph showing blood cells level changes after CAR-T infusion. CAR-T stands for chimeric antigen receptor T-cell; IL-6 stands for interleukin (IL)-6; CRP stands for C-reactive protein.
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case_images: C-reactive protein (CRP) level decreased during the first several days, followed by a slight increase, and the overall level persistently remained below the pre-infusion level ( Figure 2A ). During the whole treatment, no fever, signs of oxygen deficiency, low blood pressure, or neurological symptoms were observed, ruling out CRS and ICANS ( Figure 2B ), but severe myelosuppression had persisted after CAR-T infusion ( Figure 2C ), calling for continued promotion of hematopoietic therapy and component transfusion.
case_images: Dynamic profiling of CAR-T copies, circulating tumor DNA, and LDH after CAR-T infusion in this relapse/refractory diffuse large B cell lymphoma patient. (A) Volatility curve of CAR-T copies at the indicated time points after CAR-T infusion. (B) Line chart showing AF changes and mutations of circulating tumor DNA after infusion. (C) Graph showing the changes in LDH level after CAR-T infusion. CAR-T stands for chimeric antigen receptor T-cell; LDH stands for lactate dehydrogenase; AF stands for allele frequency.
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case_images: The overall level of CAR-T copies maintained between 6.12x101/mug DNA and 3.25x104/mug DNA within 1 month after infusion, reflecting relatively low and transient CAR-T proliferation ( Figure 3A ). Furthermore, new gene alterations of ctDNA, including CCT6B and SETBP1 were first detected on day 35 ( Figure 3B ). We also monitored the levels of LDH, a marker of tumor burden, observing a relatively synchronous increase as shown in  Figure 3C .
case_images: The whole process of multiline therapies and disease status of the patient after he was diagnosed with DLBCL. CT stands for computed tomography; PET-CT stands for positron emission tomography-computed tomography; ASCT stands for autologous stem cell transplantation; CAR-T stands for chimeric antigen receptor T-cell.
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case_images: Unfortunately, the patient got no response and developed rapid clinical deterioration during hospitalization and died 40 days after CAR-T therapy ( Figure 4 ).