Tumor Lysis Syndrome

Tumor lysis syndrome occurs as a result of the rapid release of intracellular contents into the bloodstream, leading to life-threatening concentrations. If the resulting metabolic abnormalities remain uncorrected, renal failure may develop followed by sudden death.

Etiology and Risk Factors

Tumor lysis syndrome most commonly develops during the rapid growth phase of high-grade lymphomas and leukemia in patients with high leukocyte counts; it is less common in patients with solid tumors. The syndrome is often iatrogenic, caused by cytotoxic chemotherapy. Because of clinicians’ increased awareness of the tumor lysis syndrome during the past decade and the use of adequate prophylaxis before initiation of chemotherapy, there are fewer cases currently. Occasionally, the syndrome occurs following treatment with irradiation, glucocorticosteroids, tamoxifen, or interferon.

The typical patient at risk for tumor lysis syndrome tends to be young (< 25 years of age) and male and has an advanced disease stage (often with abdominal disease) and a markedly elevated lactate dehydrogenase level.

Other predisposing factors include volume depletion, concentrated acidic urine pH, and excessive urinary uric acid excretion rates.

Signs and Symptoms

The syndrome is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and often, oliguric renal failure.

Diagnosis

The diagnosis of tumor lysis syndrome is based on the development of increased levels of serum uric acid, phosphorus, and potassium; decreased levels of serum calcium; and renal dysfunction following chemotherapy.

Prognosis

The prognosis varies depending on the adequate correction of metabolic abnormalities and the underlying etiology of tumor lysis.

Treatment

Prophylactic measures

Patients at risk for tumor lysis syndrome should be identified before the initiation of chemotherapy and should be adequately hydrated and given agents to alkalinize the urine. Treatment with allopurinol (intravenous or oral) may be instituted to minimize hyperuricemia. The recommended dosage of intravenous allopurinol ranges from 200 to 400 mg/m²/d. This regimen should be started 24 to 48 hours before the initiation of cytotoxic treatment. The dose may be equally divided into 6-, 8-, or 12-hour increments, but the final concentration should not exceed 6 mg/mL. (For oral dosages of allopurinol and intravenous doses of rasburicase, see the section on hyperuricemia treatment earlier in this chapter.)

Serum electrolytes, uric acid, phosphorus, calcium, and creatinine levels should be checked repeatedly for 3 to 4 days after chemotherapy is initiated, with the frequency of monitoring dependent on the clinical condition and the risk profile of the patient.

Established tumor lysis

Once tumor lysis is established, treatment is directed at vigorous correction of electrolyte abnormalities, hydration, and hemodialysis (as appropriate in patients with renal failure).