PMC9549058_01
Infusion of anti-CD19 CAR-T cells and allo-HSC. (A)Anti-CD19 CAR design and the schematic clinical treatment protocol for anti-CD19 CAR-T cell therapy. The scFv region that recognizes CD19 was derived from the FMC63 monoclonal antibody. The CAR contained a 4-1BB costimulatory domain and a CD3zeta T-cell activation domain (top panel). Clinical treatment protocol (bottom panel). (B)Levels of cytokines after CAR-T cell therapy. (C)Levels of ferritin after CAR-T cell therapy.(D)Dynamic white blood cell and lymphocyte numbers after CAR-T cell therapy. (E)Copies of lentivirus-containing CAR-T cells in the peripheral blood and bone marrow after CAR-T cell therapy. (F)CAR-T cells and B-cells after CAR-T cell therapy. (G)Ratio of CD4+/CD8+ T cells in the peripheral blood after CAR-T cell therapy.
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Figure 1A ). Following the infusion, the patient experienced grade 4 cytokine release syndrome (CRS) with elevated IL-6, IL-10, IFN-gamma, and ferritin levels, as well as grade 3 CAR-T cell-related encephalopathy syndrome according to Lee's grading system. The levels of IL-6, IL-10, IFN-gamma, and ferritin gradually returned to baseline 3 weeks after treatment with tocilizumab (monoclonal antibody against the IL-6 receptor) (8 mg/kg, qd, +3 and +5 days), dexamethasone (20 mg, qd, +6 to +8 days, +12 to +15 days, +19 to +21 days), and plasma exchange (2000 mL per time, +10 days, +11 days and +17 days) ( Figures 1B, C ). Figure 1D . Furthermore, lentivirus copies with the polymerase chain reaction test to reflect CAR-T cell infusion increased in relation to the B lymphocyte decline, suggesting that the CAR-T cells reached peak levels after 2 weeks ( Figures 1E, F ). In addition, the CD4+/CD8+ T cell ratio in the peripheral blood was significantly below normal 2-3 weeks after the CAR-T cell infusion ( Figure 1G ). The engraftment time of neutrophils was +36 days, and the engraftment time of platelets was +42 days after CAR-T cells infusion ( Figure 1D ).
Hepatic function and skin changes after CAR-T cell infusion. (A)Hepatic function after CAR-T cell infusion. Expression of total bilirubin (TBIL; normal range, 0-21 microM), direct bilirubin (DBIL; normal range, 0-5 microM), indirect bilirubin (IBIL; normal range, 0-15 microM), alanine transaminase (ALT; normal range, 5-40 U/L), aspartate transaminase (AST; normal range, 8-40 U/L), total protein (TP; normal range, 64-83 g/L), and albumin (normal range, 34-48 g/L) after CAR-T cell infusion. (B)Skin pigmentation and a festering skin rash after CAR-T cell infusion.
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However, decreased liver function with skin pigmentation and a festering skin rash was noted ( Figure 2 ).