. 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 3.

Differential Diagnoses of CAR-T Related Toxicities.

Clinical Presentation	Diagnoses	Comments
Respiratory failure^29,30,31	• Pneumonia • Diffuse alveolar hemorrhage • Cardiogenic pulmonary edema • “On-target, off-tumor” toxicity	• Empiric antimicrobial treatment and supportive care. • “On-target, off-tumor” has been described in CARs. Normal tissues express the tumor antigen that CARs are designed to recognize, causing direct tissue injury. Reports include gastrointestinal tract, liver, lung and cardiac toxicity.⁴⁴
Shock^29,32	• Neutropenic sepsis and septic shock • Cardiogenic shock (acute coronary syndrome, cardiac tamponade, “on-target, off-tumor”) • Hemorrhagic shock	• Empiric antibiotic treatment and supportive care of the neutropenic septic patient is recommended • Evaluate cardiac function and for signs of overt bleeding
Encephalopathy³²	• Intracranial hemorrhage or ischemic stroke • Medication induced (eg: opiates,antibiotics, anxiolytics, anti-psychotics) • Septic encephalopathy • Multi-organ failure • Meningitis	• Neurotoxicity associated with CAR has specific symptoms such as dysgraphia, inattentiveness, aphasia and lip smacking. Therefore neurological assessment should always include these specific signs for CAR-T toxicity
Liver failure⁵	• Medication induced • Hypoperfusion • Infectious hepatitis • Hemophagocytic lymphohistiocytosis • “On-target off tumor” toxicity • Portal vein thrombosis or veno-occlusive disease	• Diagnosis of HLH should require referral or consultation with a specialist as diagnosis can be challenging and the experience in this patient population is limited.
Acute renal failure^32,33	• Medication induced • Tumor Lysis syndrome • Obstructive uropathy	• Monitoring and management of tumor lysis syndrome should not differ from any other oncological patient