. Author manuscript; available in PMC: 2022 Sep 23.

Published in final edited form as: Crit Care Med. 2018 Sep;46(9):1402–1410. doi: 10.1097/CCM.0000000000003258

Table 4.

Risk factors for severity of Cytokine Release Syndrome and Neurotoxicity.

Risk Factor	Comments
Tumor Burden	Higher activation and proliferation of CAR-T cells is observed with high tumor burden leading to an exaggerated inflammatory response and higher toxicity^4,5,9,13,16.
Cell dosing	A higher dose of cells can lead to increased cytokine release, and therefore greater toxicities once these cells are activated^18,24.
Comorbidities	Higher number of comorbidities has been associated with increased risk and severity of CRS¹⁷.
Age	Although there are no definitive studies, older patients may have a lower tolerance to CRS and neurotoxicity^4,17.
Chemotherapy regimen	The chemotherapy regimen prior to cell infusion is important to ensure replication and survival of CAR T cells. A regimen that leads to severe immunosuppression and therefore an exaggerated proliferation of CAR T cells can result in increased toxicity ^9,18,24,.
Timing of onset of symptoms	Early onset of symptoms is associated with worse toxicity and should lead to more aggressive monitoring and treatment^5,24.
Cell product	Variabilities of the cell construct between protocols can potentially have an effect on cell proliferation and activity. Some factors include the costimulatory domain used, vector utilized, time in culture and type of culture⁹.