Complications

Complication
Timeframe
Likelihood
variable
high

Cytokine release syndrome (CRS) is the most significant adverse effect of chimeric antigen receptor T-cell (CAR T-cell) therapy, and affects people ages 25 or under the most severely.[184][185] It is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction. CRS signs and symptoms include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. 

Myocardial ischemia and venous thromboembolism can be provoked during CAR-T cell therapy.

Decreased left ventricular systolic function and cardiogenic shock have been reported in CAR T-cell clinical trials.[186]

Cardiovascular complications, including hypertension, atrial fibrillation, and ventricular arrhythmias (with related sudden cardiac death) have been reported in patients receiving Bruton tyrosine kinase inhibitors.[157][158][159]​​[160][161]​ These events have occurred particularly in patients with cardiac risk factors (e.g., hypertension and diabetes mellitus) or a previous history of cardiac arrhythmias, and in patients with acute infections.

variable
high

R-CHOP is relatively well tolerated, with the main toxicities being hematologic (from bone marrow suppression), infection (from neutropenia), cardiac (from doxorubicin), alopecia, infusion-related respiratory symptoms (with or without bronchospasm), chills, fever, and hypotension from rituximab.[156]

Myelosuppression (from multiple agents)

Immunosuppression leading to infections (alemtuzumab, fludarabine)

Mucositis (high-dose methotrexate)

Renal failure (from tumor lysis syndrome, carboplatin, high-dose methotrexate)

Conjunctivitis (high-dose cytarabine)

Congestive heart failure (high-dose cyclophosphamide; anthracycline-induced cardiotoxicity: e.g., from doxorubicin)

Pneumonitis (high-dose methotrexate)

Hemorrhagic cystitis (cyclophosphamide, ifosfamide)

Peripheral neuropathy (vinca alkaloids: e.g., vincristine)

Pancreatitis (cytarabine)

Hand-foot syndrome (high-dose cytarabine)

Rhinitis (cyclophosphamide)

Syndrome of inappropriate secretion of antidiuretic hormone (vincristine, vinblastine, vinorelbine, cyclophosphamide)

Secondary acute myeloid leukemias (alkylating agents: e.g., cyclophosphamide; topoisomerase II inhibitors: e.g., etoposide; and doxorubicin)

Acute promyelocytic leukemia (etoposide)

Myelodysplastic syndrome (alkylating agents, topoisomerase II inhibitors).

variable
high

Inflammation (e.g., pneumonitis)

Secondary leukemias, such as acute lymphocytic leukemia and acute myeloid leukemia

Myelodysplastic syndrome

Solid malignancy.

variable
high

Graft-versus-host disease

Hepatic veno-occlusive disease.

variable
medium

A life-threatening treatment complication of Burkitt lymphoma. It occurs due to rapid cell destruction and release of intracellular contents into the circulation. Without prompt treatment, patients may undergo renal failure and sudden death. Risk factors are rapidly growing tumor, youth (<25 years), male sex, advanced-stage disease (often abdominal), markedly elevated lactate dehydrogenase (LDH), volume depletion, concentrated acidic urine, and excessive urinary uric acid excretion.

Blood tests will reveal hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, oliguric renal failure. Prophylaxis includes allopurinol (intravenous or orally) started 24 to 48 hours before cytotoxic treatment. LDH, chemistry, uric acid, phosphorus, potassium, and calcium should be monitored.

Treatment for TLS includes correction of electrolyte abnormalities, fluid replacement, and dialysis.

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