Complications
Cytokine release syndrome (CRS), neurotoxicity, and T-cell malignancies may occur with chimeric antigen receptor (CAR) T-cell therapies, and can be fatal or life-threatening.[135][136][137]
CRS is the most significant adverse effect of CAR T-cell therapy, and affects people aged 25 or under most severely.[215][135] It is an acute systemic inflammatory syndrome characterised by fever and multiple organ dysfunction. CRS signs and symptoms include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Tocilizumab is recommended for the management of patients with prolonged or severe CAR T-cell-associated CRS.[135]
Cardiovascular complications (including myocardial ischaemia, venous thromboembolism, decreased left ventricular systolic function, and cardiogenic shock) may also occur with CAR T-cell therapy.[138][139]
Cardiovascular complications of Bruton's tyrosine kinase (BTK) inhibitor therapy include hypertension, atrial fibrillation, and ventricular arrhythmias (with related sudden cardiac death).[187][188][189][190][191] 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. Clinical evaluation of cardiac history and function should be performed prior to initiating BTK inhibitors. Patients should be carefully monitored for cardiac arrhythmias and signs of deterioration of cardiac function during treatment, and clinically managed as appropriate. The risks and benefits of initiating or continued treatment with BTK inhibitors should be carefully assessed; alternative treatment may need to be considered.
R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) is relatively well tolerated, with the main toxicities being haematologic (bone marrow suppression), infection (neutropenia), cardiac (from doxorubicin), alopecia, infusion-related respiratory symptoms (with or without bronchospasm), chills, fever, and hypotension (from rituximab).[186]
Hepatitis B virus (HBV) reactivation may occur with chemotherapy and/or rituximab treatment in NHL patients with HBV infection (i.e., positive for HBV surface antigen, or prior history HBV infection regardless of surface antigen positivity). Prophylactic antiviral therapy is recommended to prevent HBV reactivation.[70]
Other chemotherapy-related complications are listed below:
Myelosuppression and neutropenia (multiple agents)
Immunosuppression leading to infections (alemtuzumab, fludarabine)
Mucositis (high-dose methotrexate)
Gastrointestinal toxicity and hepatotoxicity (high-dose methotrexate)
Renal failure (tumour lysis syndrome, carboplatin, high-dose methotrexate)
Conjunctivitis (high-dose cytarabine)
Congestive heart failure (high-dose cyclophosphamide, anthracycline-induced cardiotoxicity e.g., doxorubicin)
Pneumonitis (high-dose methotrexate)
Haemorrhagic 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 leukaemias (alkylating agents e.g., cyclophosphamide; topoisomerase II inhibitors e.g., etoposide; and doxorubicin)
Acute promyelocytic leukaemia (etoposide)
Myelodysplastic syndrome (alkylating agents, topoisomerase II inhibitors).
Inflammation (e.g., pneumonitis)
Secondary leukaemias, such as acute lymphocytic leukaemia and acute myeloid leukaemia
Myelodysplastic syndrome
Solid malignancy.
An oncological emergency, particularly among patients with Burkitt's lymphoma.
Use vigorous hydration (with intravenous fluids), phosphate-binding agents, and hypouricaemic agents (e.g., allopurinol, rasburicase) to prevent or treat TLS.
TLS is characterised by hyperkalaemia, hyperphosphataemia, hyperuricaemia, and hypocalcaemia, which can occur following treatment for NHL (or spontaneously in rare cases), particularly if WBC count (tumour burden) is high. Close monitoring is essential.
TLS can lead to cardiac arrhythmias, seizures, acute renal failure, and death, if untreated.
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