Table 1. Common grading systems for cytokine release syndrome and neurologic toxicity.
| Grading of Toxicity | Cytokine release syndrome | Neurologic toxicity | |||
|---|---|---|---|---|---|
| UPenn Grading Scale | Lee Grading Scale | CTCAE Grading Scale¶ | Neelapu Grading Scale | ||
| Grade 1 | Mild reaction | Mild reaction; infusion interruption not indicated; intervention not indicated | Mild | CARTOX-10* score 7–9 (mild impairment) | |
| Grade 2 | Moderate reaction, with signs of organ dysfunction (e.g., gr2 Cr or gr3 LFTs) not attributable to any other conditions | Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours | Moderate | CARTOX-10 score 3–6 (moderate impairment) | |
| Grade 3 | More severe reaction and organ damage (e.g., gr3 Cr or gr4 LFTs) not attributable to any other conditions; includes hypotension treated with intravenous fluids or low-dose vasopressors, coagulopathy requiring fresh frozen plasma or cryoprecipitate or fibrinogen concentrate, and hypoxia requiring supplemental oxygen (nasal cannula oxygen, high-flow oxygen, CPAP, or BiPAP) | Severe symptoms including any one or more of the following: | Severe | CARTOX-10 score 0–2 (severe impairment), or Stage 1–2 papilledema#, or CSF opening pressure <20 mmHg, or partial seizure, or non-convulsive seizures on EEG with response to benzodiazepine | |
| ❖ A drop in blood pressure of 20% or more from the patient’s; baseline not | |||||
| ❖ Responsive to fluid therapy within 24 hours or not responsive to IV fluid bolus of at least 20 mL/kg; | |||||
| ❖ Gr 3 Respiratory dysfunction; | |||||
| ❖ Gr 3 Cr indicative of renal dysfunction; | |||||
| ❖ Gr 3 neurologic dysfunction | |||||
| Grade 4 | Life threatening complications, such as needing high-dose pressors or mechanical ventilation | Life-threatening consequences; vasopressor or ventilator support indicated | Life-threatening | Patient in critical condition, and/or obtunded and cannot perform assessment of tasks, or stage 3–5 papilledema, or CSF opening pressure ≥20 mmHg, or cerebral edema, or generalized seizures, or status epilepticus, or new motor weakness | |
| Grade 5 | Death | Death | Death | Death | |
¶, in terms of levels of consciousness, orientation, ability to perform activities of daily living (in the con-text of encephalopathy), speech, tremors, seizures, incontinence, and motor weakness. The final grade is the highest grades of all the items evaluated; *, CARTOX-10 scale: one point is assigned for each of the following tasks that is performed correctly (normal cognitive function is defined by an overall score of 10): orientation to year, month, city, hospital, and President/Prime Minister of country of residence (total of 5 points); name three objects—for example, point to clock, pen, button (maximum of 3 points); write a standard sentence, for example, ‘our national bird is the bald eagle’ (1 point); count backwards from 100 in tens (1 point); #, papilledema grading is performed according to the modified Frisén scale (34). CTCAE, Common Terminology Criteria for Adverse Events; Gr, grade; Cr, creatinine; LFT, liver function test; CARTOX-10, CAR-T-cell-therapy-associated toxicity 10-point neurological assessment. CSF, cerebrospinal fluid.