Table 2.

Major CAR Treatment Related Side Effects for B-ALL Patients.

CAR Treatment Related Side Effects	Incidence	Complications	Treatment Strategies	References
B cell Aplasia	-Develops in most patients, especially when the treatment against the leukemic B cells is effective (patients in CR)	-Decreased B cell counts -Hypogammaglobulinemia -Severe infections if untreated	-IV administration of immunoglobulin (IG replacement therapy)	[10,11,12,13,14]
CRS	-Develops in many patients, correlates with strong CAR-T cell response, usually occurring within time of max cell expansion -Some grade of CRS can develop in over 75% of B-ALL patients	-High levels of pro-inflammatory cytokines such as IL-6 and IL-1 -Symptoms of cytokine storm -Very high fever, headache, fatigue, myalgia, organ dysfunction, etc.	-Common monitoring practices in the ICU until resolution (only if severe) -Analgesics, vasopressors, IV fluids, etc. -Tocilizumab (IL-6 receptor antagonist) -Siltuximab (IL-6 antibody) -IL-1 blockade -Anti-inflammatory drugs (methylprednisolone)	[12,13,15]
CNS Neurotoxicity	-Very wide range of incidence between studies (varies between no cases to majority of cases in a study) -Commonly coincides with strong CRS response, however can develop in absence of CRS as well	-More mild cases can include headaches, disorientation, memory and attention loss, impaired speech/writing, etc. -More severe cases can include seizures, encephalopathy, impaired motor and movement functions, coma, etc.	-Common monitoring practices in the ICU until resolution (only if severe) -Levetiracetam for certain neurological symptoms -Corticosteroids -Using strategies to reduce CRS response as contributing factor can help	[12,13,15,17]

B-ALL = B cell acute lymphocytic leukemia, CAR = chimeric antigen receptor, CNS = central nervous system, CR = complete remission, CRS = cytokine release syndrome, ICU = intensive care unit, IG = immunoglobulin, IV = intravenous.