Table 3:
Cytokine Release Syndrome (CRS) Grading Scales [153]
| CRS | Lee criteria [154] | CTCAE [59] | Penn [155] | ASTCT [156] | Treatment Considerations |
|---|---|---|---|---|---|
| Grade 1 (Mild) | Not life-threatening, fever, constitutional symptoms (e.g., nausea, fatigue, myalgias, headache) | Mild reaction, tachycardia | Prodromal syndrome Mild reaction treated with supportive care |
Temperature ≥ 38° C | Monitoring Supportive care (e.g., antipyretics, antiemetics) Infusion interruption not recommended Assess for other causes (e.g., infection) |
| Grade 2 (Moderate) | Oxygen requirement < 40% OR Hypotension responsive to fluids or low dose of one vasopressor Grade ≥ 2 organ toxicity |
Stable dysrhythmias Hypotension responsive to fluid resuscitation or low dose vasopressors for < 24 hours Prophylactic medications indications for < 24 hours |
Moderate reaction – hypoxia, fever, mild hypotension. Signs of organ dysfunction (elevated Cr, LFTs) | Temperature ≥ 38° C Hypotension not requiring vasopressor OR hypoxia requiring low-flow nasal cannula or blow-by (≤ 6 L/minute. |
Supportive care Hospitalization for management of CRS-related symptoms IV fluids or low dose vasopressors Therapy interruption recommended Consider tocilizumab +/− corticosteroids |
| Grade 3 (Severe) | Oxygen requirement >= 40% OR Hypotension requiring high dose or multiple vasopressors Grade ≥ 3 organ toxicity OR Grade ≥ 4 transaminitis |
Prolonged reaction Unstable dysrhythmias Shock: requiring high dose vasopressors or multiple vasopressors for > 24 hours Signs of hypoperfusion Recurrence of symptoms following initial improvement |
Hospitalization required for management of organ dysfunction Hypotension treated with IV fluids or vasopressors Coagulopathy requiring FFP or cryoprecipitate Hypoxia requiring supplemental oxygen |
Temperature ≥ 38° C with hypotension requiring a vasopressor or hypoxia Requiring high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask. |
Supportive care Hospitalization required High dose or multiple vasopressors. Mechanical ventilation Tocilizumab +/− corticosteroids (second line) |
| Grade 4 (Life-threatening) | Requirement for ventilator support OR Grade ≥ 4 organ toxicity (excluding transaminitis) |
Life-threatening dysrhythmias Refractory shock requiring multiple vasopressors Ventilator support indicated Cardiomyopathy: LVEF < 20% |
Resistant CRS, no clinical improvement within 12–18 hours or worsening at any time despite prior management. Hypotension requiring high dose vasopressors Hypoxia requiring mechanical ventilation |
Temperature ≥ 38° C with hyotension requiring multiple vasopressors (excluding vasopressin). OR hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation and mechanical ventilation) |
Supportive care Multiple vasopressors Mechanical ventilation Tocilizumab Corticosteroids Consider third line therapy or alternative measures |
| Grade 5 | Death | Death | Death | Death |
Based on CRS experience (Guidelines from NCI Experimental Transplantation and Immunology Branch), consider IL-6 inhibitor (e.g., tocilizumab) use if: LVEF < 40% by echocardiogram, NE requirement >=2 ug/min for 48 hours since the first administration of NE, SBP of 90mmHg that cannot be maintained by NE, O2 requirement of FiO2 > 50% or more for more than 2 hours continuously [157]. ASTCT consensus guidelines: Low flow: ≤ 6 L/minute