| CRS | ICANS |
---|---|---|
Symptoms & Signs | Onset: Fever with other constitutional symptoms (myalgias, malaise, nausea, vomiting, diarrhea, etc.) Progression: Hypotension, hypoxia, tachycardia, tachypnea, arrhythmia, pleural effusion, capillary leak, coagulopathy, pulmonary edema, DIC and multiorgan failure [7, 155, 216] Accompanied infections [217] L-CRS (in NHL): Local swelling and redness [43] | Onset: Somnolence, disorientation, inattention, tremor, expressive aphasia, dysgraphia and apraxia [84, 218] Progression: Globe aphasia, cognitive disturbance, focal motor and sensory defects, seizures, fatal cerebral edema and intracranial hemorrhage [155, 219] |
Timing | Onset: 1–9 days after CAR T-cells infusion Duration: | Onset: 2–9 days after CAR T-cells infusion Duration: |
Cytokine profile | Serum: IFN-γ, IL-15, IL-6, IL-10, GM-CSF, IL-1RA, IL-2, IP-10 IL-1β, IL-8, and TNF CSF: Similar to the cytokine profile in the serum, except for higher levels of IL-8, IP-10, and MCP-1 [45, 222] | |
Risk factors | Patient Characters: Disease type (ALL), high disease burden, preexisting thrombocytopenia and endothelial activation Characters of CAR T-cell products: Targeting CD19, CD28 costimulatory domain, receiving fludarabine and cyclophosphamide, high infusion dose, peak serum CAR T-cells levels [146, 223] | Patient Characters: CRS, disease type (ALL), high disease burden, preexisting thrombocytopenia and endothelial activation, preexisting neurologic comorbidities Characters of CAR T-cell products: Targeting CD19, CD28 costimulatory domain, receiving fludarabine and cyclophosphamide, high infusion dose, peak serum CAR T-cells levels [146, 223] |
Grading criteria* | •Temperature ≥ 38.0 °C •Hypotension (based on vasopressor) •Hypoxia | •ICE score (for adults and children> 12 years) or CAPD (for children≤12 years) •Depressed level of consciousness •Seizures •Motor findings •Elevated intracranial pressure/cerebral edema |
Management | •Antipyretics, IV hydration, anti-infective treatment •Tocilizumab, corticosteroids •ICU treatment, vasopressor support, supplemental O2 [224] •Symptomatic treatment for L-CRS (e.g. drainage of serous effusion, airway protection, regulation of intestinal flora) [43] | •Supportive management •EEG, neuroimaging •Tocilizumab (only when concurrent with CRS), corticosteroids, anti-epileptics drugs •ICU treatment, airway protection, specific neurointensive treatment [224] |