More on Cytokine Release Syndrome toxicities a... - CLL Support

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More on Cytokine Release Syndrome toxicities associated with CAR-T-cell therapy.

Jm954 profile image
Jm954Administrator
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May 2019, not specific to CLL but adds to our understanding of CAR-T treatment. Extracted from a paper comparing neurological CRS grading assessments.

CRS is caused by the release of cytokines during in vivo CART cell expansion. The toxicity of CRS results from the systemic effects of cytokines on multiple organ systems.

Severe CRS causes toxicity beyond fever, hypotension responsive to fluids, and hypoxia responsive to low-level oxygen support. The likelihood of a patient experiencing severe CRS depends on patient-, tumor-, and CART-related factors.

In terms of patient-related factors, the baseline inflammatory state appears to be of particular importance, so patients with a high baseline serum ferritin, c-reactive protein, or elevated baseline cytokine levels are at a higher risk of CRS.

It appearsthat CRS is somewhat different depending on disease type and a higher tumor burden also appears to predict a higher rate of CRS.

The rate of CRS may also be modifiable by CART design or manufacturing practices, or may be different based on the costimulatory domain used (i.e., CD28 vs. 4-1BB).

Finally, earlier interventions with treatments such as corticosteroids and anti-interleukin 6 (IL-6) therapy (i.e., tocilizumab) appear to reduce the rates of severe CRS.

Jackie

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DriedSeaweed profile image
DriedSeaweed

Can you please add link? I will see if my library can upload it to my account today.

Jm954 profile image
Jm954Administrator in reply toDriedSeaweed

sciencedirect.com/science/a...

DriedSeaweed profile image
DriedSeaweed in reply toJm954

thanks!

Smakwater profile image
Smakwater

For sure, those pesky cytokines.

Aside from CAR T, I wish there was a simple affordable test measuring cytokine involvement for CLL patients.

It would answer allot of "I wonder if's " that we we all experience during W&W.

It would also prevent some of the self experimentation that occurs when we are trying to find relief from unexplainable aggravations.

JM

Jm954 profile image
Jm954Administrator in reply toSmakwater

Yep, I agree as these tests are expensive and rarely done outside the research setting.

Jackie

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