Clinical tumor lysis syndrome includes increased serum creatinine, cardiac dysrhythmia or sudden death, or a seizure. Rapid lysis of tumor cells can be associated with a large tumor burden, with cytotoxic chemotherapy, or radiation therapy in the setting of a malignancy with a high proliferative rate.

Hyperuricemia is a result of the breakdown of purine nucleic acids and must be addressed. Historically, the xanthine oxidase inhibitor allopurinol has been employed to lower the peak uric acid level and to prevent uric acid nephropathy.²⁰ Allopurinol treatment leads to the accumulation of hypoxanthine and xanthine. Because xanthine is less soluble than uric acid, it can precipitate in the renal tubules. Urinary alkalinization increases the solubility of uric acid but not of xanthine. This therapy for tumor lysis syndrome has the potential to form xanthine crystals resulting in obstruction of renal tubules.¹⁸

Clinical manifestations of tumor lysis syndrome include nausea, vomiting, diarrhea, lethargy, anorexia, seizures, tetany, cramps, syncope, and sudden death. Urinalysis can show urate crystals. An ECG should be performed in patients with serious electrolyte abnormalities.

CRITICAL DECISION

What is the appropriate treatment for tumor lysis syndrome?

Treatment includes aggressive intravenous hydration at approximately 2 to 3 liters/m2 per day to keep urine output at 80 to 100 mL/m2 per hour. Potassium should be withheld from hydration fluids initially because of the risk of hyperkalemia; calcium should be withheld because of the risk of calcium phosphate precipitation. Urinary alkalinization has the potential disadvantage of promoting calcium phosphate deposition in the kidney and elsewhere.²¹

The usual allopurinol dose in adults to address hyperuricemia is 100 mg/m2 every 8 hours, initiated 24 to 48 hours before chemotherapy and continued for up to 1 week.²¹ An alternative to allopurinol is rasburicase, a recombinant urate oxidase, which catalyzes the degradation of uric acid and rapidly lowers serum uric acid levels. It is effective in preventing and treating hyperuricemia and in treating tumor lysis syndrome.²² It may be given at a dose of 0.15 to 0.2 mg/kg in 50 mL of isotonic saline infused over 30 minutes once daily for 5 to 7 days but is FDA-approved only for pediatric patients. Serum levels of calcium, phosphate, uric acid, potassium, creatinine, and lactate dehydrogenase should be monitored.

Hyperphosphatemia can be treated with aluminum hydroxide, a phosphate binder, and restriction of phosphate intake. Dialysis can be necessary to treat persistent hyperphosphatemia, hypocalcemia, or low urine output. The best management is prevention via intravenous hydration and with hypouricemic agents.²¹