Fig. 2
Predominant cerebral cytokine release syndrome (CRS) manifestations after CART19 therapy. a Wave changes in body temperature after CART19 infusion, with a maximum temperature per 24-h period indicated by the squares. b Heterogeneous structures with punctiform nodal or linear enhancement in the cerebellar sulcus and hidden parts (arrows) by contrast-enhanced MRI on day 5 after CART19 infusion, indicating the local infiltration of inflammatory cells. c Inflammatory cytokine levels in peripheral serum and CSF, respectively, at different time points. CSF cytokine concentrations were extremely higher than in the serum, with IFN-γ levels 20 times higher and IL-6 levels 190 times higher. d Mononuclear cell (MNC) counts and protein levels in CSF and profiles of cerebrospinal pressure at different times of CNSL and cerebral CRS after CART19 infusion. As indicated, the patient suffered three times of recurrent CNSL, with the highest MNC counts (300/μL) and protein levels (0.19 g/μL) in CSF and a higher cerebrospinal pressure (265 mmH2O). During CRS, the CSF contained higher levels of protein (4.0 g/μL) and less amount of WBCs (20/μL). e CSF cells were predominantly CD3+ T cells with few CD19+ B cells by FACS analysis which did not support a diagnosis of CNSL. For leukoencephalopathy, MRI imaging usually discloses bilateral and symmetric white matter areas of hyperintense signal on T2-weighted and fluid-attenuated inversion recovery images and signs of restricted diffusion; CSF usually contains a slight increase of WBC counts and protein levels. Thus, leukoencephalopathy was not considered. Routine CSF cultivation and specific virus DNA detection excluded bacteria, virus, and fungal infection