Table 3.
The American Society for Transplantation and Cellular Therapy (ASTCT) grading system and management strategy for immune effector cell associated neurotoxicity syndrome (ICANS) for adults [Table adapted from Yakoub-Agha et al. (22) and Neill et al. (104)].
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
|---|---|---|---|---|
| ICE score* | 7–9 | 3–6 | 0–2 | Unable to perform |
| Depressed level of consciousness | Awakens spontaneously | Awakens to voice | Awakens only to tactile stimulus | Unarousable or requires vigorous or repetitive tactile stimuli to arouse. Stupor or coma |
| Seizure | No | No | Any clinical seizure that resolves rapidly or non-convulsive seizures on EEG that resolve with intervention | Life-threatening prolonged seizure (>5 min) or repetitive clinical or electrical seizures without return to baseline in between |
| Motor findings | No | No | No | Deep focal motor weakness such as hemiparesis or paraparesis |
| Elevated ICP/cerebral edema | No | No | Focal/local edema on neuroimaging | Diffuse cerebral edema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI palsy; or papilledema; or Cushing’s triad# |
| ICU | Alert ICU | Transfer to ICU | Transfer to ICU | Transfer to ICU |
| Investigations | Neurological examinations including fundoscopy to exclude papilledema, EEG, MRI, and lumbar puncture in absence of contraindications | |||
| Management | Alert neurologist, elevate the head of the patient’s bed to 30°, management of CRS if concurrent | |||
| Close monitoring | Dexamethasone IV 10 mg every 6 h, and consider levetiracetam 750 mg bid as prophylaxis for seizures | Dexamethasone IV 20 mg every 6 h. If seizure, clonazepam IV 1mg or other benzodiazepines to terminate it, then loading with levetiracetam | Management of seizure as per grade 3. If papilledema, start acetazolamide IV 1,000 mg followed by 250–1,000 mg bid. If elevated ICP/cerebral edema, consider hyperosmolar therapy with mannitol and hyperventilation. Methylprednisolone IV 1,000 mg/d. Evaluation of other experimental salvage options | |
CRS, cytokine release syndrome; EEG, electroencephalography; ICE, immune effector cell associated encephalopathy; ICP, intracranial pressure; ICU, intensive care unit; IV, intravenous; MRI, magnetic resonance imaging.
*Orientation to year, month, city, hospital: 4 points; Ability to name 3 objects: 3 points; Ability to follow simple commands: 1 point; Ability to write a standard sentence: 1 point; Ability to count backward from 100 by 10: 1 point.
#Irregular, decreased respirations, Bradycardia, Systolic hypertension.