Grading schemes for cytokine release syndrome
| Grading scale . | Grade 1 . | Grade 2 . | Grade 3 . | Grade 4 . |
|---|---|---|---|---|
| CTCAEv4 (blinatumomab) | Mild | Infusion interruption indicated but responds promptly to symptomatic treatment (eg, antihistamines, nonsteroidal anti-inflammatory drug, narcotics, intravenous fluids); prophylactic medications indicated for ≤ 24 h | Prolonged (eg, not rapidly responsive to symptomatic medications and/or brief interruption of infusion); recurrence of symptoms after initial improvement; hospitalization indicated for clinical sequelae (eg renal impairment, pulmonary infiltrates) | Life-threatening consequences; pressor or ventilator support |
| No infusion interruption | ||||
| No intervention | ||||
| 2014 NCI Consensus | Symptoms are not life-threatening and require symptomatic treatment only; eg fever, nausea, fatigue, headache, myalgias, malaise | Symptoms require and respond to moderate intervention | Symptoms require and respond to aggressive intervention | Life-threatening symptoms; requirement for ventilator support or grade 4 organ toxicity (excluding transaminitis) |
| Oxygen requirement < 40% or hypotension responsive to fluids or low-dose pressors or grade 2 organ toxicity | Oxygen requirement < 40% or hypotension requiring high-dose or multiple pressors or grade 3 organ toxicity or grade 4 transaminitis | |||
| UPENN/CHOP | Mild reaction treated with supportive care only | Moderate reaction requiring intravenous therapies or parenteral nutrition; mild signs of organ dysfunction (creatinine ≤grade 2 or liver function tests ≤grade 3) | More severe reaction, requiring hospitalization; moderate signs of organ dysfunction (grade 3 creatinine or grade 4 liver function tests) related to CRS; hypotension treated with intravenous fluids or low-dose pressors; hypoxemia requiring oxygenation, bilevel positive airway pressure, or continuous positive airway pressure | Life-threatening complications, including hypotension requiring high-dose vasoactives or hypoxemia requiring mechanical ventilation |
| Hospitalization for CRS or febrile neutropenia | ||||
| Comparisons across scales | CTCAE: linked to infusion of drug, not applicable to cellular therapy. | CTCAE: linked to infusion/withholding of a drug, not applicable to cellular therapy. | Grade 3 NCI permits more severe hypotension compared with a UPENN/CHOP grade 3. | Life-threatening hypoxia (mechanical ventilation) similar across scales. |
| NCI and UPENN/CHOP allow for symptom management; CTCAE does not | Grade 2 NCI permits more severe hypoxia and hypotension compared with a UPENN/CHOP grade 2 |
| Grading scale . | Grade 1 . | Grade 2 . | Grade 3 . | Grade 4 . |
|---|---|---|---|---|
| CTCAEv4 (blinatumomab) | Mild | Infusion interruption indicated but responds promptly to symptomatic treatment (eg, antihistamines, nonsteroidal anti-inflammatory drug, narcotics, intravenous fluids); prophylactic medications indicated for ≤ 24 h | Prolonged (eg, not rapidly responsive to symptomatic medications and/or brief interruption of infusion); recurrence of symptoms after initial improvement; hospitalization indicated for clinical sequelae (eg renal impairment, pulmonary infiltrates) | Life-threatening consequences; pressor or ventilator support |
| No infusion interruption | ||||
| No intervention | ||||
| 2014 NCI Consensus | Symptoms are not life-threatening and require symptomatic treatment only; eg fever, nausea, fatigue, headache, myalgias, malaise | Symptoms require and respond to moderate intervention | Symptoms require and respond to aggressive intervention | Life-threatening symptoms; requirement for ventilator support or grade 4 organ toxicity (excluding transaminitis) |
| Oxygen requirement < 40% or hypotension responsive to fluids or low-dose pressors or grade 2 organ toxicity | Oxygen requirement < 40% or hypotension requiring high-dose or multiple pressors or grade 3 organ toxicity or grade 4 transaminitis | |||
| UPENN/CHOP | Mild reaction treated with supportive care only | Moderate reaction requiring intravenous therapies or parenteral nutrition; mild signs of organ dysfunction (creatinine ≤grade 2 or liver function tests ≤grade 3) | More severe reaction, requiring hospitalization; moderate signs of organ dysfunction (grade 3 creatinine or grade 4 liver function tests) related to CRS; hypotension treated with intravenous fluids or low-dose pressors; hypoxemia requiring oxygenation, bilevel positive airway pressure, or continuous positive airway pressure | Life-threatening complications, including hypotension requiring high-dose vasoactives or hypoxemia requiring mechanical ventilation |
| Hospitalization for CRS or febrile neutropenia | ||||
| Comparisons across scales | CTCAE: linked to infusion of drug, not applicable to cellular therapy. | CTCAE: linked to infusion/withholding of a drug, not applicable to cellular therapy. | Grade 3 NCI permits more severe hypotension compared with a UPENN/CHOP grade 3. | Life-threatening hypoxia (mechanical ventilation) similar across scales. |
| NCI and UPENN/CHOP allow for symptom management; CTCAE does not | Grade 2 NCI permits more severe hypoxia and hypotension compared with a UPENN/CHOP grade 2 |