Cytokine release syndrome (CRS), sometimes referred to as a cytokine storm, is a systemic inflammatory response triggered by a variety of reasons such as infections, certain drugs, or after treatment with some types of immunotherapy, (e.g., monoclonal antibodies and CAR-T cells). It is characterized by a large, rapid release of cytokines into the blood. Cytokines are small proteins that help cells around the body communicate. When the immune system detects a threat, cells release cytokines to coordinate the body’s response. Too many cytokines cause harmful levels of inflammation throughout the body. Symptoms of CRS may include nausea, headache, tachycardia, hypotension, rash, shortness of breath, or in severe cases, death.
Chimeric Antigen Receptor T (CAR-T) Cell Therapy is an advancement in the treatment of relapsed or refractory leukemia and large b-cell lymphoma. In some instances complications of the therapy have been observed. Two of the most prevalent complications are Cytokine Release Syndrome (CRS) and Immune effector Cell Associated Neurotoxicity Syndrome (ICANS).
In 2019, the American Society for Transplantation and Cellular Therapy (ASTCT) published a paper regarding the formal consensus for grading both CRS and ICANS. With this new consensus on grading, unique ICD-10-CM diagnosis codes were created to more effectively track the severity of patient symptoms in response to immune effector cell (IEC) therapy.
The following table summarizes the new grading based on the consensus paper in the References. For additional information, see the consensus paper (see References below).
Requiring high-flow nasal cannula3, facemask, nonrebreather mask, or Venturi mask
Requiring positive pressure (eg, CPAP, BiPAP, intubation and mechanical ventilation)
Fever is defined as temperature ≥38°C not attributable to any other cause. In patients who have CRS then receive antipyretic or anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia.
CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For example, a patient with temperature of 39.5°C, hypotension requiring 1 vasopressor, and hypoxia requiring low-flow nasal cannula is classified as grade 3 CRS.
Low-flow nasal cannula is defined as oxygen delivered at ≤6L/minute. Low flow also includes blow-by oxygen delivery, sometimes used in pediatrics.
High-flow nasal cannula is defined as oxygen delivered at >6L/minute.
Grade 5 (G89.8335) is defined as death due to CRS in which another cause is not the principle factor leading to this outcome.
It should be noted that, although ICD-10-CM codes were requested which further describe the grade levels for Immune effector cell-associated neurotoxicity syndrome (ICANS), at the time of publication there are no new codes for that syndrome.
ICD-10-CM instructional notes specify that any underlying cause (e.g., complications following infusion and therapeutic injection [T80.89-], complications of transplanted organs and tissue [T86.-]) should be coded before using these new D89.83- codes. Associated manifestations should also be coded.
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