Table 3.

Grade 5 Toxicities Associated with CD19 CAR T Cells.

Disease	Target	Toxicity	Reference
Chronic lymphocytic leukemia (NCT00466531)	CD19	One death related to CAR T cells Low-grade sepsis was the most likely trigger in this heavily pretreated immunosuppressed patient but also considered the possibility that a cyclophosphamide-induced cytokine storm may have enhanced the in vivo activation of modified T cells	R. Brentjens et al. (2010)
Lymphoma (NCT02631044)	CD19	One death related to CAR T cells Diffuse alveolar damage	Plieth (2017)
Adult acute lymphoblastic leukemia (NCT01044069)	CD19	Three deaths related to CAR T cells Severe hypotension and CRS Status epilepticus and CRS Sepsis and multi-organ failure	Plieth (2017)
Adult acute lymphoblastic leukemia (NCT02535364)	CD19	Five deaths related to CAR T cells Cerebral edema	Plieth (2017)
Relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, or acute lymphoblastic leukemia (NCT01865617)	CD19	Six deaths One CRS One cerebral edema Two CRS or neurotoxicity One CRS, cerebral edema One encephalopathy and pontine hemorrhage	Plieth (2017)
Lymphoma (NCT02348216)	CD19	Three deaths Hemophagocytic lymphohistiocytosis Cardiac arrest in the setting of CRS, later specified as anoxic brain injury CRS, multi-organ failure leading to cerebral edema	Plieth (2017)
Adult acute lymphoblastic leukemia (NCT02614066)	CD19	One death CRS	Plieth (2017)
Lymphoma (NCT02030834)	CD19	One death Encephalitis possibly related to the CAR product	Plieth (2017)
Adult acute lymphoblastic leukemia and lymphoma (NCT02030847 and NCT01029366)	CD19	Three deaths CRS and infection (Influenza B, pseudomonas infection, or stenotrophomonas infection)	Teachey et al. (2016); Plieth (2017)
Pediatric acute lymphoblastic leukemia (NCT02435849)	CD19	One death Cerebral hemorrhage	Plieth (2017)

Note: CAR = chimeric antigen receptor; CD = cluster of differentiation; CRS = cytokine release syndrome.