PMC10067676_01
Positron emission tomography-computed tomography performed before CAR-T cell therapy showing multiple lymphoma lesions including in the pericardium (arrows).
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At this time a PET-scan found systemic multiple lymphoma localizations with hepato-splenic, bone, abdominal and thoracic lesions as well as pericardial hypermetabolism and a small aortic cross hematoma (Figure 1).
Clinical course following CAR-T cell injection (A) and ICU admission (B). AF, atrial fibrillation; AP, arterial pressure; BT, body temperature; CRS, cytokine release syndrome; DAP, diastolic AP; HR, heart rate; ICANS, immune effector cell-associated neurotoxicity syndrome; ICU, intensive care unit; MAP, mean AP; SAP, systolic AP.
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On day 4, due to persistence of fever, tocilizumab (8 mg/kg/day) was initiated (Figure 2A). The time course of the vital signs and medications following ICU admission is shown in Figure 2B.
Electrocardiogram at ICU admission showing atrial fibrillation and right bundle branch block (A) and computed tomography performed after CAR-T cell therapy showing major circumferential pericardial effusion (arrows) (B).
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An ECG showed atrial fibrillation, right bundle branch block but no sign of pericarditis (Figure 3A). No intracranial or thoracic bleeding was detected, but an increase in pericardial effusion was noted (Figure 3B).
Evolution of CAR-T cell absolute number (A) and percentage of total lymphocytes (B) following injection, in blood (blue dots and line) and in pericardial fluid (red dot). Flow cytometry analysis of blood (C) and pericardial fluid (D) according to size (SS INT LIN) and CD45 expression (CD45-KrOr). Black ovals represent lymphocyte population. The black rectangle represents lymphoma population only present in pericardial fluid. Among lymphocyte population, CAR-T cells were selected according to CD3 and CD19 Fc-biotine expression in blood (E) and pericardial fluid (F). Colors from blue to red indicate an increase in cell count.
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Evolution of CAR-T cell expansion was similar to that in most patients with a peak at around day 10 after reinjection (Figures 4A,B). Detection of CAR-T cells was based on size, and CD45+ CD3+ CD19+ FCbiot+ cell expression (Figures 4C-F). Pericardial fluid analysis, performed with the same method, showed 26,841 cells/microl, of which 98% were lymphoma cells (small size CD45- CD19+ CD3- CD56+ DR+) and 2% were lymphocytes (CD45+), of which 72.8% (310 cells/microL) were CAR-T cells with more than 80% of activated cells (DR+) (Figures 4D,F). The concomitant analysis of blood showed no lymphoma cells and 880/microL of lymphocytes of which 88.7% were CAR-T cells with more than 90% of activated cells (Figures 4C,E). In blood, detection of CAR-T cells decreased rapidly after day 15 (Figures 4A,B).