Table 1.

Cytokine release syndrome (CRS) following CAR-T therapy: grading and clinical presentation.

	Penn Criteria	Lee Criteria	ASTCT Criteria
Grade 1	Mild reaction (supportive care)	Symptoms are not life-threatening and require symptomatic treatment only (fever, nausea, fatigue, headache, myalgias, malaise)	Temperature ≥ 38 °C, no hypotension, no hypoxia
Grade 2	Moderate reaction: signs of organ dysfunction related to CRS and not attributable to any other condition. Hospitalization for management of CRS-related symptoms, including neutropenic fever and need for IV therapies (not including fluid resuscitation for hypotension)	Symptoms require and respond to moderate intervention: oxygen requirement < 40% FiO2, hypotension responsive to IV fluids or low dose of one vasopressor	Temperature ≥ 38 °C, with hypotension not requiring vasopressors, and/or hypoxia requiring low-flow nasal cannula
Grade 3	Hospitalization required for management of symptoms related to organ dysfunction. Hypotension treated with multiple fluid boluses or low-dose vasopressors. Coagulopathy requiring fresh frozen plasma, cryoprecipitate, or fibrinogen concentrate. Hypoxia requiring supplemental oxygen (nasal cannula oxygen, high-flow oxygen, non-invasive ventilation)	Symptoms require and respond to aggressive intervention: oxygen requirement ≥ 40% FiO2, hypotension requiring high-dose or multiple vasopressors, moderate organ toxicity, or transaminitis	Temperature ≥ 38 °C, with hypotension requiring vasopressors with or without vasopressin, and/or hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask, or venturi mask
Grade 4	Life-threatening complications such as hypotension requiring high-dose vasopressors. Hypoxia requiring mechanical ventilation	Life-threatening symptoms: requirement for ventilator support, severe organ toxicity	Temperature ≥ 38 °C, with hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia requiring positive pressure (non-invasive ventilation or mechanical ventilation)