Table 2:

Summary of cytokine release syndrome grading systems.

CRS Grading	CTCAE v4[23]	CTCAE v5[24]	Lee, et al. [14]	Porter, et al.[26]
Grade 1	Mild reaction; infusion interruption not indicated; intervention not indicated	Fever with or without constitutional symptoms	Symptoms are not life threatening and require symptomatic treatment only, eg, fever, nausea, fatigue, headache, myalgias, malaise	Mild reaction: Treated with supportive care such as anti-pyretics, anti-emetics
Grade 2	Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤ 24 hours	Hypotension responding to fluids; hypoxia responding to <40% O2	Symptoms require and respond to moderate intervention Oxygen requirement <40% or Hypotension responsive to fluids or low dose of one vasopressor or Grade 2 organ toxicity	Moderate: Requiring IV therapies or parenteral nutrition; some signs of organ dysfunction (i.e. gr 2 Cr or gr 3 LFTs) related to CRS and not attributable to any other condition. Hospitalization for management of CRS related symptoms including fevers with associated neutropenia
Grade 3	Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates)	Hypotension managed with one pressor; hypoxia requiring ≥ 40% O2	Symptoms require and respond to aggressive intervention Oxygen requirement ≥40% or Hypotension requiring high dose or multiple vasopressors or Grade 3 organ toxicity or grade 4 transaminitis	More severe reaction: Hospitalization required for management of symptoms related to organ dysfunction including gr 4 LFTs or gr 3 Cr related to CRS and not attributable to any other conditions; excludes management of fever or myalgias. Includes hypotension treated with intravenous fluids or low-dose pressors, coagulopathy requiring FFP or cryoprecipitate, and hypoxia requiring supplemental O2 (nasal cannula oxygen, high flow O2, CPAP or BiPAP). Patients admitted for management of suspected infection due to fevers and/or neutropenia may have grade 2 CRS.
Grade 4	Life-threatening consequences; pressor or ventilatory support indicated	Life-threatening consequences; urgent intervention indicated	Life-threatening symptoms Requirement for ventilator support or Grade 4 organ toxicity (excluding transaminitis)	Life-threatening complications such as hypotension requiring “high dose pressors”, hypoxia requiring mechanical ventilation.

Abbreviations: NSAIDS: non-steroidal anti-inflammatory drugs, LFTs: liver function tests, CRS: cytokine release syndrome, Cr: creatinine, FFP: fresh frozen plasma, CPAP: continuous positive airway pressure, BiPAP: bilevel positive airway pressure