PMC8316683_01
Timeline of diagnosis and treatment.
fonc-11-706431-g001.jpg
PMC8316683_01_fonc-11-706431-g001.jpg
f1
A few days later (October 19), SARS-CoV-2 was detected in a PCR test of a routine nasal/pharyngeal swab sample ( Figure 1 ). However, the patient developed intermittent episodes of fever (38.5 C maximum) and still had SARS-CoV-2 replicates measurable in nasal/pharyngeal swab samples repeated every 3 to 4 days (CT values, 27-30;  Figure 1 ). Considering the worsening clinical situation and rising LDH serum concentrations as signs of progressive DLBCL, leukapheresis for CAR T-cell production was ultimately planned regardless of SARS-CoV-2 persistence as determined in PCR tests from nasal/oropharyngeal samples every 3 to 4 days (CT- values, 28-30;  Figure 1 ). Although SARS-CoV-2 PCR assays from nasal/pharyngeal swabs were negative, SARS-CoV-2 could be detected in bronchoalveolar lavage (BAL) samples at high concentrations (CT value, 28 in BAL;  Figure 1 ).
Computed tomography (CT) of the lungs in frontal (A) and transverse sections (B). Disseminated ground-glass opacities due to COVID-19 pneumonia (December 2020).
fonc-11-706431-g002.jpg
PMC8316683_01_fonc-11-706431-g002.jpg
f2
Chest CT scan demonstrated immensely progressive ground-glass opacities ( Figure 2 ).
Positron emission tomography with (A, C) and without computed tomography co-registration (B, D) in ventral (A, C) and dorsal view (B, D). Disseminated manifestations of diffuse large B-cell lymphoma refractory to chemoimmuntherapiy prior to CAR-T cell therapy (A, B) and in remission three months after anti-CD19 CAR-T treatment with axi-cel.
fonc-11-706431-g003.jpg
PMC8316683_01_fonc-11-706431-g003.jpg
f3
A PET-CT scan performed with (18)F-labelled fluoro-deoxy-d-glucose (FDG) prior to CAR T-cell treatment demonstrated a massive progression of DLBCL with disseminated lymphoma manifestations and explaining the clinical symptoms ( Figures 3A, B  ). Whole-body PET-CT scan 1 and 3 months later (days +30 and +90) showed a complete response (CR) with only residual lymph nodes without metabolic activation ( Figures 3C, D  ).
Quantification of CD19-CAR gene sequences in peripheral blood by ddPCR. CD19-CAR (axi-cel) gene sequences were quantified by digital-droplet (dd) PCR. In brief, genomic DNA was extracted from peripheral blood mononuclear cells at different time points after infusion of axi-cel. DdPCR was carried out to detect FMC63-28Z-1 amplicons as recently published by our group.
fonc-11-706431-g004.jpg
PMC8316683_01_fonc-11-706431-g004.jpg
f4
The side effects and clinical response were in agreement with the expansion of anti-CD19 CAR T-cells in quantifications by ddPCR, as has recently been reported by our group ( Figure 4 ).