CRS glossary of terms

Adjudication

A structured review to decide, consistently, whether a CRS event occurred and how severe it was, often by independent reviewers.³

Anticytokine therapy

Drugs that block the inflammatory proteins (cytokines) driving CRS. Tocilizumab is the main example.¹

Antipyretic

A fever-reducing medication (e.g., acetaminophen).⁴

ASTCT grading

The standard 1–4 CRS severity scale from the American Society for Transplantation and Cellular Therapy. It is the field’s common reference for how severe an event is.¹

CAR T-cell therapy (CAR-T)

A treatment that re-engineers a patient’s own T cells to attack cancer. It is a common trigger of CRS.⁴

Constitutional symptoms

Whole-body symptoms like fever, chills, fatigue, and body aches, rather than symptoms tied to one organ.¹

Corticosteroid

An anti-inflammatory drug (e.g., dexamethasone) used for more severe CRS.⁴

Cytokine release syndrome (CRS)

A supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms can be progressive, must include fever at onset, and may include hypotension, capillary leak (hypoxia), and end-organ dysfunction.¹

CRS recurrence

A new CRS event, meeting ASTCT onset criteria, occurring after a previously documented CRS event has met the CRS resolution definition.

CRS resolution

A patient with CRS in whom fever, oxygen, and pressor requirements have resolved for 24 hours is assumed to have resolved CRS, unless there are alternative causes for the fever, hypoxia, and/or hypotension.¹

Cytokine

A signaling protein released by immune cells. A flood of these (“cytokine release”) drives CRS.⁴

Endpoint adjudication

Independent, standardized review of key trial events so they are classified consistently across sites and studies.³

Fever

Temperature ≥ 38°C not attributable to any other cause.¹

Grade 1 CRS

Fever (≥ 38.0°C) with or without constitutional symptoms.¹

Grade 2 CRS

Fever (≥ 38.0°C) with hypotension not requiring vasopressors and/or hypoxia requiring low-flow nasal cannula (≤ 6 L/min) or blow-by. Fever is not required if CRS has previously been documented and antipyretic or anticytokine therapy has been received.¹

Grade 3 CRS

Fever (≥ 38.0°C) with hypotension requiring one vasopressor with or without vasopressin, and/or hypoxia requiring high-flow nasal cannula (>6 L/min), facemask, nonrebreather mask, or venturi mask, not attributable to any other cause. Fever is not required if CRS has previously been documented and antipyretic or anticytokine therapy has been received.¹

Grade 4 CRS

Fever (≥ 38.0°C) with hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, mechanical ventilation), not attributable to any other cause. The use of multiple vasopressors constitutes Grade 4 CRS irrespective of total cumulative dose. Fever is not required if CRS has previously been documented and antipyretic or anticytokine therapy has been received.¹

HLH/MAS

Hemophagocytic lymphohistiocytosis / macrophage activation syndrome. A severe overactive immune response that can look like or overlap with CRS.¹

Hypotension (grading criteria)

A disorder characterized by blood pressure below the normal expected level for an individual in a given environment.² An individual requiring IV fluid boluses or vasopressors to maintain normal blood pressure may be considered to have hypotension.¹

Hypoxia (grading criteria)

A disorder characterized by a decrease in the level of oxygen in the body.² For CRS grading, an individual requiring supplemental oxygen to correct an oxygenation deficit is considered to have hypoxia; oxygen given only as a comfort measure should not inform CRS grade.¹

ICANS

Immune effector cell-associated neurotoxicity syndrome. Neurological effects (e.g., aphasia, altered level of consciousness, seizures) that can occur alongside or instead of CRS.¹

Immune effector cell therapy

Treatments that direct the immune system’s effector cells (like T cells) against cancer. CAR-T and T-cell engagers are examples.¹

Infusion-related reaction (IRR)

A reaction during or shortly after an infusion. It is distinct from CRS and usually earlier in timing.²

Prospective documentation

Recording data in real time as events happen, rather than reconstructing them later.

Retrospective adjudication

Reviewing and classifying events after they have occurred, using existing records.

Sepsis

A dangerous, body-wide response to infection. It is a key alternative to rule out when CRS is suspected.¹

Supportive care

Treatment that stabilizes the patient and manages symptoms (fluids, oxygen, fever control) rather than targeting the cancer itself.⁴

T-cell engager (TCE)

A drug (often a bispecific antibody) that links a patient’s T cells to cancer cells, with timing that can differ from CAR-T because of step-up dosing.¹

Tocilizumab

The usual first-line drug for CRS. It blocks the IL-6 cytokine.¹

Tumor lysis syndrome (TLS)

Metabolic disturbances from rapid cancer-cell breakdown. Another condition to distinguish from CRS.²

Vasopressor support

Medications that raise dangerously low blood pressure. Needing them can signal more severe CRS.¹