108-Prevention and management of tumour lysis syndrome (2024)

Early risk assessment and institution of appropriate prophylaxis to prevent TLS is essential. Adequate hydration and maintenance of urine output is the mainstay of prevention and pre-emptive administration of hypouricaemic agents should be considered.
Consideration should be given todelaying treatment in high risk patients until prophylactic measures can be commenced. If a delay is not appropriate, then ensure patient is managed in an ICU or haematology/oncology unit with staff with the appropriate expertise and skills as deemed by the local institution.
If prophylactic measures fail and clinical TLS develops, institutional guidelines for the management of hyperkalaemia, hyperphosphataemia and hypocalcaemia, as well as other clinical manifestations, need to be initiated immediately.

Hydration

Increased hydration and enhanced urinary flow promotes urinary excretion of uric acid and phosphate. A 2008 International Expert Panel on TLSr recommended vigorous hydration in patients at intermediate or high risk of TLS and those presenting with LTLS or CTLS prior to treatment.r

Unless contraindicated aim to hydrate with 3 L/m²/day of IV fluid.
Continue for several days to maintain a urine output of at least 100 mL/m²/hour and a urine specific gravity of less than or equal to 1.010 g/mL.rr
Weigh twice daily and maintain strict fluid balance chart.
Diuretics may be used to maintain urine output if necessary, but should not be required in patients with relatively normal renal and cardiac function and are contraindicated in patients who are hypovolaemic or have obstructive uropathy.
Potassium, calcium and phosphate should not initially be added to hydration fluids to avoid exacerbation of the hyperkalaemia, hyperphosphataemia and calcium phosphate precipitation that may occur once tumour break down begins.

Urinary alkalinisationr

Urinary alkalinisation with sodium bicarbonate is NOT currently recommended as there is a lack of clear evidence demonstrating benefit. The only available experimental study suggested that hydration with saline alone is as effective as alkalinisation in minimising uric acid precipitation.r
Urinary alkalinisation shouldbe avoidedin patients with tumour lysis syndrome, especiallywhen rasburicase is available, as alkalinisation has the potential disadvantage of promoting calcium phosphate deposition, in patients who develop marked hyperphosphataemia once tumour breakdown begins.
If alkalinisation is used, it should be initiated when the serum uric acid level is high and discontinued when hyperphosphataemia develops.
IV sodium bicarbonate shouldonlybe administered to patients with metabolic acidosis.

Hypouricaemic agents

Allopurinol

Allopurinol competitively inhibits xanthine oxidase, blocking the conversion of hypoxanthine and xanthine to uric acid. Allopurinol effectively reduces formation of new uric acid, however itdoes notreduce existing levels of uric acid. Therefore, in patients with pre-existing hyperuricaemia (serum uric acid>0.45 mmol/L) rasburicase is the preferred hypouricaemic agentr.There is a risk of acute obstructive renal failure, due to xanthine crystal deposition in the renal tubules, with allopurinol. Allopurinol also can cause skin rashes and increased liver function tests. There are also a number of clinically significant drug interactions with allopurinol including cyclophosphamide, high dose methotrexate, mercaptopurine and azathioprine (mercaptopurine and azathioprine require a 60 to 75% dose reduction if used concurrently with allopurinol).

Dosage and administration:

100 mg/m²orally every 8 hours (maximum 800 mg/day)rr
300 mg/day used in practice by majority of haematologists, however increasing allopurinol dose or switching to rasburicasemay be necessary in the presence of deteriorating biochemical or clinical markers.r
Initiate 24 to 48 hours prior to cytotoxic therapy if possible, and continue untilthree to seven days after completion, oruntil uric acid leveland other laboratory evidence of tumour lysis (e.g. elevated serum LDH levels) have normalised.
Reduce dose by 50% or more in the presence of renal failure.
Prophylactic hydration with careful monitoring is generally safe to use in patients with an allergy to allopurinol.r
Adjust dose of co-administered interacting drug(s) or allopurinol.

Rasburicase

A recombinant form of urate oxidase, rasburicase converts uric acid to allantoin which is readily excreted in the urine. It is well tolerated, rapidly lowers serum uric acid, and is effective in prevention and treatment of hyperuricemia in TLS.rNormalisation of uric acid level occurs in about four hours. There is no rationale for the use of allopurinol and rasburicase together.

Rasburicase should be considered in patients:

at intermediate or highriskof developing TLS;especially those with renal impairment and/or unable to tolerate high fluid input,
withpre-existing LTLS and/or CTLS (prior to cytotoxic therapy),
unable to tolerate orallergic to allopurinol, or
who do not adequatelyrespond to standard TLS preventive measures of hydration and allopurinol.

Dosage:

0.20 mg/kg once daily IV for 5 to 7 daysr or fixed 3 mg or 6 mgsingle IV dose (intermediateor high risk patients respectively).rr
Initiate 24 to 48 hours prior to cytotoxic therapy.

Administration:r

Dilute in 50 mL sodium chloride 0.9% and infuse IV over 30 minutes (do not use anyIVglucose solution for dilution due to potential incompatibility).
Infuse viaa different line/lumen than that used for chemotherapy; if a separate line is not available,flush wellwith saline betweenrasburicase and chemotherapy.
If weight based dosing is used, it is recommended to round the dose to the nearest 1.5 mg (available vial size) to avoid wastage(rasburicase costs ~$400 per mg).