Complications
Cytokine release syndrome (CRS) is the most significant adverse effect of chimeric antigen receptor T-cell (CAR T-cell) therapy, and affects people aged 25 or under the most severely.[171][172] 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.
Myocardial ischaemia 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.[173]
Cardiovascular complications, including hypertension, atrial fibrillation, and ventricular arrhythmias (with related sudden cardiac death) have been reported in patients receiving Bruton's tyrosine kinase inhibitors.[145][146][147][148][149] 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.
R-CHOP is relatively well tolerated, with the main toxicities being haematologic (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.[144]
Myelosuppression (from multiple agents)
Immunosuppression leading to infections (alemtuzumab, fludarabine)
Mucositis (high-dose methotrexate)
Renal failure (from tumour 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)
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.
Graft-versus-host disease
Hepatic veno-occlusive disease.
A life-threatening treatment complication of Burkitt's 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 tumour, 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 hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia, 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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