Cytokine release syndrome
Background
- Systemic inflammatory response syndrome that can be adverse effect of certain immunotherapies, such as monoclonal antibodies and CAR-T therapies (e.g. CART19 for leukemia)
- Pathophysiology and presentation similar to sepsis
- Severity ranges from mild flu-like illness to severe sepsis-like inflammatory response with shock, vascular leakage, DIC, and multi-organ system failure[1]
Clinical Features
- Mild: flu-like illness
- Severe: mimics septic shock
- Fever, tachycardia, hypotension, dyspnea, hypoxia
- Organ-specific dysfunction: encephalopathy, coagulopathy, renal failure, CHF
Differential Diagnosis
- Sepsis!
- Hemophagocytic lymphohistiocytosis
Shock
- Cardiogenic
- Acute valvular Regurgitation/VSD
- CHF
- Dysrhythmia
- ACS
- Myocardial Contusion
- Myocarditis
- Drug toxicity (e.g. beta blocker, CCB, or bupropion OD)
- Obstructive
- Air embolism
- Aortic Stenosis
- Cardiac Tamponade
- PE
- Tension pneumothorax
- Distributive
- Hypovolemic
- Severe dehydration
- Hemorrhagic shock (traumatic and non-traumatic)
Related to Local Tumor Effects
- Malignant airway obstruction
- Bone metastases and pathologic fractures
- Malignant spinal cord compression
- Malignant Pericardial Effusion and Tamponade
- Superior vena cava syndrome
Related to Biochemical Derangement
- Hypercalcemia of malignancy
- Hyponatremia due to SIADH
- Adrenal insufficiency
- Tumor lysis syndrome
- Carcinoid syndrome
Related to Hematologic Derangement
Related to Therapy
- Chemotherapy-induced nausea and vomiting
- Cytokine release syndrome
- Chemotherapeutic drug extravasation
- Differentiation syndrome (retinoic acid syndrome) in APML
- Stem cell transplant complications
- Catheter-related complications
- Tunnel infection
- Exit site infection
- CVC obstruction (intraluminal or catheter tip thrombosis)
- Catheter-related venous thrombosis
- Fracture of catheter lumen
- Oncologic therapy related adverse events
Evaluation
Hospitals administering CAR-T therapies will often have very specific guidelines for initial workup
- Immunocompromised infection workup: see neutropenic fever
- Evaluate for tumor lysis syndrome
- Labs to screen for organ dysfunction: CBC, BMP, LFTs, DIC labs
Management
- Strongly consider discussion with CAR-T treatment team
- Empiric antibiotics (assume sepsis until proven otherwise)
- Treat shock
- Corticosteroids for severe cases
- Consider Tocilizumab (IL-6 receptor antagonist) in consultation with oncology
Disposition
- Admit or consider transfer to hospital with oncology
See Also
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003181/
- Shimabukuro-vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):56.
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