Table 2 CRS grading scales: Penn grading scale, CTCAE v4.0, and 2014 Lee et al. scale

Grade 1

Mild reaction: treated with supportive care such as antipyretics, antiemetics

Mild reaction; infusion interruption not indicated; intervention not indicated

Symptoms are not life-threatening and require symptomatic treatment only, e.g., fever, nausea, fatigue, headache, myalgias, malaise

Grade 2

Moderate reaction: some signs of organ dysfunction (e.g., grade 2 creatinine or grade 3 LFTs) related to CRS and not attributable to any other condition. Hospitalization for management of CRS-related symptoms, including fevers with associated neutropenia, need for IV therapies (not including fluid resuscitation for hypotension)

Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤ 24 h

Symptoms require and respond to moderate intervention. Oxygen requirement < 40% or hypotension responsive to fluids or low-dose pressors or grade 2 organ toxicity

Grade 3

More severe reaction: hospitalization required for management of symptoms related to organ dysfunction, including grade 4 LFTs or grade 3 creatinine related to CRS and not attributable to any other conditions; this excludes management of fever or myalgias; includes hypotension treated with intravenous fluids (defined as multiple fluid boluses for blood pressure support) 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). Patients admitted for management of suspected infection due to fevers and/or neutropenia may have grade 2 CRS

Prolonged reaction (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)

Symptoms require and respond to aggressive intervention. Oxygen requirement ≥ 40% or hypotension requiring high-dose or multiple pressors or grade 3 organ toxicity or grade 4 transaminitis

Grade 4

Life-threatening complications such as hypotension requiring high-dose vasopressors, ^a hypoxia requiring mechanical ventilation

Life-threatening consequences; pressor or ventilator support indicated

Life-threatening symptoms. Requirements for ventilator support or grade 4 oxygen toxicity (excluding transaminitis)