*Tumour lysis syndrome Flashcards
Define tumour lysis syndrome. Which electrolyte abnormalities occur?
Defined as a combination of metabolic and electrolyte abnormalities occurring:
- spontaneously
- or following initiation of cytotoxic treatment in patients with cancer.
Characterised by hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia, renal failure.
In which malignancies is tumour lysis syndrome common?
It is more prevalent in malignancies with high proliferating rates, tumour burden, and chemosensitivity
- Incidence in NHL is ~6%, ALL 5.2%, AML 3.4%.
- Rarely with solid tumours e.g. breast, testicular and small cell lung cancers
- Old age may predispose due to reduced GFR
What are some risk factors for TLS?
Predisposing factors:
- High proliferation rate of cancer
- Large tumour burden
- Chemosensitivity - good response to anti-cancer treatment
- Cytotoxic chemotherapy
- Dehydration
- Renal impairment (age)
- High WCC, high serum LDH
What is the pathophysiology of TLS?
Malignant cells have
- high turnover rate
- greater nulceic acid products (–> uric acid)
- phosphate (x4 the amount of normal cells)
Rapid destruction of these cells by chemotherapy –> release of high intracellular…into blood
- uric acid --> precipitation of uric acid crystals, tubular obstruction and AKI
- potassium from cell degradation and AKI/lactic acidosis
- phosphate –> CaP crystals, precipitation, nephrocalcinosis
and secondary reduced calcium (due to hyperphosphataeamia)
What are low, intermediate and high risk groups for TLS?
Low (<1% risk) - indolent NHL, low proliferation rate malignancy.
Intermediate - diffuse large cell lymphoma, ALL with WCC 10-50, CLL with WCC 10-100, CML, multiple myeloma, solid tumours w/ rapid response to therapy.
High (>5% risk) - Burkitt’s lymphoma, lymphoblastic leukaemia, B-cell ALL, ALL with WCC >100, AML with WCC >50.
What are the signs and symptoms of TLS?
- Typically starts within 7 days of chemo initiation
Symptoms suggestive of TLS:
- N&V
- anorexia
- diarrhoea
- muscle weakness
- muscle cramps, paraesthesia
- lethargy
- laryngeal spasm
Signs:
- hyper/hypotension
- oliguria/anuria /haematuria - hyperuricaemia causing AKI
- signs of arrhythmias (syncope, chest pain, dysponoea) - K+
- hypocalcaemia, tetany, Chvostek sign, Trousseau signs, seizures - hyperphosphataemia
What investigations would you do for tumour lysis syndrome?
Bloods:
- U&Es - potassium and urea; repeat BD if abnormal
- Bone profile - for calcium and phosphate
- LDH
- FBC - elevated WBC increase TLS risk
- Creatinine - x1.5 upper limit of normal
Other:
- Urinary pH - check for hyperuricaemia before therapy
- ECG/cardiac monitoring - in presence of hyperkalaemia/hypocalcaemia
What is the laboratory criteria for TLS diagnosis?
2 or more of the following, within 3 days before or 7 days after chemotherapy:
- Uric acid >476 micromol/L or 25% increase
- Potassium >6.0 mmol/L or 25% increase
- Phosphate >2.1 mmol/L in children or >1.45 mmol/L in adults or 25% increase
- Calcium <1.75 mmol/L or 25% decrease from baseline.
What is the management of TLS?
- Aggressive hydration +/- loop diuretic to optimise renal function
- Hyperphosphataemia tx:
- binding agents e.g. aluminium hydroxide
- Hyperuricaemia tx:
- rasburicase or allopurinol
- Hyperkalaemia tx:
- if <6mmol/L give hydration, loop diuretic, sodium polystyrene sulfonate
- if >6mmol/L give Ca gluconate + insulin + dextrose. Then sodium polystyrene sulfonate
- Hypocalcaemia tx:
- do not treat if asymptomatic
- treating hyperP should treat Ca
- +/- renal dialysis if resistant to other treatments
What is the MOA of sodium polystyrene sulfonate in hyperkalaemia?
Promotes K elimination through bowel
If a patient on cancer tx is diagnosed with TLS, what long term therapy is advised?
Allopurinol
What are the main complications of TLS?
- AKI
- Arrhythmia
- Seizures - due to hypocalcaemia
- Lactic acidosis
What are some prevention strategies for TLS?
Early recognition
Stratifying patients as low, intermediate or high risk of TLS according to type of malignancy, LDH, WCC.
