The prevention and management of tumour lysis syndrome in paediatric & adolescent patients with malignant disease

• Summary of guideline
• Aims
• Background
• Diagnosis
• Prevention strategies
• Treatment/Management

Summary of Guideline

This guideline describes the prevention and management of tumour lysis syndrome (TLS) in the setting of patients under the care of the Department of Paediatric / Teenage-Young Adult Haematology and Oncology at the Leeds Children’s Hospital.

It outlines a risk stratified approach to prevention, risk reduction, detection and management of this uncommon but potentially fatal complication of malignant disease. 

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Aims

To improve the prevention, recognition and management of tumour lysis syndrome (TLS)

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Background

Tumour lysis syndrome (TLS) is a combination of metabolic derangements caused by the release of intracellular components into the blood after rapid lysis of malignant cells. This can precipitate acute kidney failure and result in hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia, with seizures, tetany and cardiac arrhythmias consequent to this.

Tumour lysis syndrome can occur spontaneously in patients with tumours of a high proliferative rate, but is more commonly seen following initiation of chemotherapy. Occasionally it can follow intense physiological stress (eg. general anaesthesia or sepsis and shock). Anticipating the problem and acting rapidly are the most important ways of stopping it progressing.

This guideline describes treatment strategies for TLS involving the appropriate management of fluids and pharmacological agents to reduce the incidence of renal failure.

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Diagnosis

Tumour lysis syndrome is an acute renal impairment secondary to the breakdown of malignant cells. It is defined by laboratory abnormalities (See Table 1).

The abnormalities can progress rapidly, and regular and close observation of renal function and biochemical parameters is essential for good prevention and management (see Table 2 for frequency).

TABLE 1: Biochemical abnormalities of tumour lysis syndrome

*Two or more of these changes satisfy the Cairo-Bishop laboratory definition of TLS

Monitoring for TLS should be undertaken by requesting the following investigations (see Table 2 for frequency)

U+Es (urea and electrolyte panel)
Calcium
Phosphate
Uric acid/Urate (unless given rasburicase)

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Prevention strategies

Prevention strategies for TLS are based upon risk stratifying malignant disease states likely to cause TLS (see Table 2 )

These risk states require appropriate tumour imaging (e.g. chest radiograph for mediastinal disease in lymphoma / leukaemia, abdominal ultrasound in abdominal lymphoma) to have been undertaken as described in the ‘initial investigations’ guidelines.

The patient should also have had routine recording of height, weight and blood pressure.

Patients with renal impairment, either pre-existing or newly diagnosed, require additional consultation with the Consultant in Paediatric Haematology/Oncology and often Paediatric Nephrology

IV Fluids - Use potassium free 0.45% sodium chloride /5% glucose to limit hyperkalaemia should TLS develop.

Note High urinary sodium concentrations are associated with urate supersaturation. Hence 0.9% sodium chloride should not be used as a hydration fluid.

No potassium supplements should be used unless serum potassium <2.6mmol/l and it MUST BE DISCUSSED with the Consultant before commencing any potassium or other electrolyte supplementation.

Allopurinol - see BNFc for information

Rasburicase - High risk patients are initially treated using rasburicase as a single dose at 0.2mg/kg.

Once an appropriate response is achieved patients should start allopurinol. For patients whose biochemical markers remain elevated and who remain at risk of TLS further daily doses of rasburicase may be considered.

Once chemotherapy is initiated the patient’s biochemical markers should be monitored for TLS and subsequent doses of rasburicase administered if required. Subsequent doses would be indicated if biochemical markers of TLS worsen; discuss such patients with the Consultant overseeing care. Patients may receive rasburicase if they have already had doses of allopurinol the same day however no clinical benefit is obtained from using both agents in combination.

Rasburicase should be administered a maximum of once daily. No minimum time is needed between doses of allopurinol and rasburicase.

Patients who fail to respond to rasburicase should be reviewed and considered for renal dialysis

Prescribing

Rasburicase should be prescribed as a once only medicine in the appropriate section of the drug chart. (December 2015 - paediatric charts ‘once only’ section is on the front.) . Each dose of rasburicase should be prescribed individually after a daily review of the patient’s requirement for further doses.

Contra-indications

Contra-indicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and other cellular metabolic disorders known to cause haemolytic anaemia

Use with caution in patients with a history of atopic allergy i.e. asthma as rasburicase can precipitate allergic responses resulting in skin rashes and bronchospasm

Renal/Hepatic Impairment

No dose adjustments are required for renal or hepatic impairment

Administration

Dose added to 50-100mls^ of 0.9% sodium chloride as an IV infusion over 30 minutes.

In order to maximise the cost effectiveness of treatment doses should be made up from vial combination detailed in the table below

^ (The volume is unimportant & intended to allow staff to allow the patient to receive the drug over 30 mins by whatever delivery method is appropriate.)

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Treatment / Management

Established tumour lysis syndrome can be fatal.

The following section is to guide management - decisions should be informed by this but discussed with the Consultant in Paediatric Haematology/Oncology and often Paediatric Nephrology.

General statement
Patients who present with signs of TLS on admission or who develop biochemical abnormalities suggestive of TLS should receive rasburicase as a stat dose if not given in the preceding 24 hours.

Once an appropriate response has been achieved the patient should receive prophylactic allopurinol until chemotherapy begins.

Hyperphosphataemia:
Increase hydration progressively to 3.5 l/m²/day then 4 l/m²/day, driving urine output with furosemide 1-2mg/kg (maximum single dose 40mg up to 8 hourly) as necessary*. Consider ‘capping’ fluids in very large patients (e.g. surface area>2.5 m²).

Severe Hyperkalaemia (serum K >5.5):

• MUST start cardiac monitoring with ECG
• Immediately contact the Consultant in Paediatric Haematology/Oncology
• See Hyperkalaemia guideline

Hypokalaemia:
This is likely to be secondary to hyper-hydration.

Do NOT reduce fluid intake without discussing with Consultant in Paediatric Haematology/Oncology OR give potassium supplements without discussion with Consultant.

If serum potassium concentration under 2.6 mmol/l discuss with Consultant*.

Renal failure:
This is a difficult situation which will require discussion with the Consultant in Paediatric Haematology/Oncology and Paediatric Nephrology, and often PICU.

Plasma haemofiltration is useful if fluid overload is the major problem, with peritoneal dialysis as the first choice in the face of uncontrollable biochemical disturbance.