Tumor Lysis Syndrome

© TLS is a metabolic disorder caused by rapid cell destruction (usually during chemotherapy treatment for cancer) and associated with several electrolyte disturbances, notably hyperuricemia.

TLS is most commonly associated with the chemothera-peutic treatment of cancers, such as leukemias and lymphomas. These types of cancers have a large tumor cell burden and are highly sensitive to destruction by chemotherapy. Massive lysis of intracellular contents occurs including the breakdown of nucleotides into hypoxanth-ine, xanthine and, eventually, uric acid. These large amounts of uric acid overwhelm normal urinary excretion capacities and can undergo crystalline precipitation. This can lead to acute renal failure and a host of electrolyte disturbances including hyper-

kalemia and hyperphosphatemia. If not prevented or treated early, TLS can lead to acute kidney damage and perhaps death; thus TLS is considered an oncologic emergency. The incidence of TLS varies according to definition, tumor type, and patient characteristics but is thought to be approximately 5% in high-risk cancers.

Due to the potential severity of TLS, strategies to prevent this disorder are mandatory in susceptible patients. Aggressive hydration (usually with isotonic fluids such as 0.9% saline) and diuresis are the cornerstones of TLS prevention. This strategy promotes the excretion of uric acid before crystallization occurs. Some authors also recommend alkalinization of the urine, which increases the solubility of uric acid.

However, investigations of this modality have failed to show a clear benefit, and re-

cent practice guidelines do not recommend its routine use.

Allopurinol has a crucial role in the prevention of TLS. The IV formulation reduces uric acid levels in high-risk patients by as much as 57% and can prevent hyperuri-

cemia in up to 90% of patients treated. Unfortunately, allopurinol does not reduce levels of uric acid formed before treatment, and the IV formulation can cause adverse effects similar to the oral form.

Rasburicase is a recombinant form of urate oxidase indicated for the prevention and treatment of TLS in pediatric patients. This enzyme converts uric acid to the more soluble compound allantoin. This potent agent can dramatically reduce uric acid levels in patients at high risk.34 Rasburicase is well tolerated; mild cutaneous hyper-sensitivity reactions are the most common adverse effect. It can also cause hemolys-is, especially in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Rasburicase has a higher acquisition cost than IV allopurinol, and some investigators have studied lower doses of the drug or use it preferentially in patients with existing renal insufficiency or uric acid levels greater than 10 mg/dL (590 ^mol/L).

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