Tumour Lysis Syndrome (TLS) Flashcards
what is tumour lysis syndrome (TLS)?
- an oncological emergency that occurs when malignant cells rapidly break down, releasing their contents into the bloodstream
- this causes significant changes to the levels of electrolytes within the blood and can be life-threatening if not recognised and treated
- most commonly occurs in patients with lymphoproliferative malignancies after initiation of treatment
what is the aetiology of TLS?
- most commonly occurs after the initiation of chemotherapy, particularly in regimes that include cell cycle phase-specific drugs
- typically occurs between 12-72 hours after treatment is given
what metabolic and electrolyte abnormalities can occur due to rapid cancer cell breakdown during chemotherapy?
- hyperuricaemia (e.g. due to the breakdown of nucleic acids)
- hyperphosphataemia
- hypocalcemia (e.g. secondary to hyperphosphataemia)
- hyperkalaemia
can tumour lysis syndrome (TLS) occur without chemotherapy?
- rare
- spontaneous TLS can occur in high-grade haematological malignancies with a very high cell turnover rate
which malignancies have a higher risk of tumour lysis syndrome (TLS)?
- poorly differentiated lymphomas (e.g. burkitt lymphoma, high-grade NHL)
- leukaemia (e.g. AML, ALL, CML)
- fast-growing solid tumours (e.g. HCC, SLCC, breast cancer)
what are the other risk factors for TLS?
- age
- large tumour burden
- LDH >1,500 IU
- extensive bone marrow involvement
- high tumour sensitivity to chemotherapy
- specific chemotherapy agents (e.g. cisplatin, etoposide, fludarabine, intrathecal methotrexate, paclitaxel, rituximab, radiation, interferon, corticosteroids, tamoxifen)
- pre-existing renal impairment
- dehydration
- concurrent use of nephrotoxic agents
what are the symptoms of TLS?
- nausea
- vomiting
- confusion
- muscle cramps
- tetany
- diarrhoea
- lethargy
- oliguria
- syncope
- chest pain
- palpitations
what are the investigations for the diagnosis and monitoring of TLS?
- ECG (e.g. hyperkalaemia, hyperphosphataemia or hypocalcaemia)
- urine pH (e.g. hyperuricaemia)
- FBC
- U&Es
- bone profile
- uric acid
- LDH
what is the laboratory definition of TLS?
defined as two or more of the following occurring 3 days before to 7 days after cancer treatment initiation:
- uric acid ≥476 micromol/L (≥8 mg/dL) or 25% increase from baseline
- potassium ≥6 mmol/L or 25% increase from baseline
- phosphate ≥1.45 mmol/L or 25% increase from baseline
- calcium ≤1.75 mmol/L or 25% decrease from baseline
what is the clinical definition of TLS?
diagnosed in patients who meet the criteria for laboratory TLS and at least one of the following:
- increase in serum creatinine ≥1.5 times the ULN
- cardiac arrhythmia
- seizure
- sudden death
how is a patient at low risk of TLS managed?
- regular monitoring of blood tests (e.g. U&Es, bone profile, uric acid, LDH)
- monitor fluid balance
- consider allopurinol if hyperuricaemia is present before starting chemotherapy treatment (e.g. 300mg for 7 days, to start 2 days before chemotherapy treatment)
how is a patient at intermediate risk of TLS managed?
- regular monitoring of blood tests (e.g. U&Es, bone profile, uric acid, LDH), including 1-2 times daily for the first three days of treatment and daily after that
- intravenous hydration with normal saline for two days before treatment; aim to maintain urine output 100 mL/m²/hour
- allopurinol should be given to patients with hyperuricemia; if allopurinol does not reduce serum uric acid, consider rasburicase
how is a patient at high risk of TLS managed?
- regular monitoring of blood tests (e.g. U&Es, bone profile, uric acid, LDH), including 3-4 times daily after starting treatment
- intravenous hydration with normal saline for two days before treatment; aim to maintain urine output 100 mL/m²/hour)
- rasburicase should be given to patients with hyperuricaemia
what is the general management of tumour lysis syndrome (TLS)?
- IV fluids (e.g. maintain urine output >100 mL/m²/hour)
- basic observations (e.g. at least 4-6 hourly)
- daily weights
- blood tests (e.g. every 6 hours)
- ECG
how are electrolyte abnormalities in tumour lysis syndrome (TLS) managed?
- hyperuricaemia: IV rasburicase for 3-7 days
- hyperkalaemia: calcium gluconate + glucose/insulin infusion
- hyperphosphataemia: phosphate-binding agents can be considered
- hypocalcaemia: IV calcium gluconate
what are the long-term complications of TLS?
- AKI (e.g. due to calcium phosphate deposition and uric acid)
- cardiac arrhythmias (e.g. due to hyperkalaemia and/or hypocalcaemia)
- seizures (e.g. due to hypocalcaemia and/or hyperphosphataemia)
- lactic acidosis (e.g. due to chemotherapy-induced cell death and AKI)
