Tumor Lysis Syndrome Resolution Criteria

Question

A 47-year-old man with newly diagnosed Burkitt lymphoma developed laboratory tumor lysis syndrome 2 days after his first cycle of chemotherapy and was treated with aggressive intravenous hydration and a single dose of rasburicase. Five days later he is alert, has no cramps, tetany or arrhythmia, and urine output is 1.5 mL/kg per hour. Blood pressure is 124/76 mm Hg and heart rate is 84 beats/min. Laboratory studies now show uric acid 250 µmol/L, creatinine 105 µmol/L, potassium 4.2 mmol/L, phosphate 1.3 mmol/L, corrected calcium 2.30 mmol/L, bicarbonate 24 mmol/L and a falling lactate dehydrogenase. The oncology team is deciding whether the metabolic picture has recovered enough to give the next cycle. Which of the following sets of criteria best indicates readiness to resume chemotherapy?

Accepted Answer

A. Uric acid below 476 µmol/L, creatinine below 141 µmol/L, normal potassium and phosphate — Tumor lysis syndrome results from massive release of intracellular potassium, phosphate and nucleic acids from lysing tumor cells, producing hyperkalemia, hyperphosphatemia, hyperuricemia and secondary hypocalcemia, with acute kidney injury from uric acid and calcium phosphate crystal deposition. Cytotoxic therapy is resumed only once those derangements have resolved, and the operative benchmark is the Cairo and Bishop laboratory definition, which sets uric acid at 476 µmol/L (8 mg/dL) or above, potassium at 6.0 mmol/L or above, and phosphate at 1.45 mmol/L or above as abnormal, with clinical tumor lysis requiring a creatinine of at least 1.5 times the upper limit of normal, roughly 141 µmol/L in an adult man. Falling below all of those values, as this patient has, means the syndrome has resolved biochemically and renal function has recovered, so the next cycle can proceed with continued hydration and monitoring. Insisting on a uric acid below 178 µmol/L is stricter than any published criterion, is below the normal reference range, and would needlessly delay treatment of a highly proliferative and chemosensitive malignancy in which delay itself is dangerous. Targeting a urine pH above 8 is wrong on two counts: routine urinary alkalinization has been abandoned by the 2008 international expert panel and the 2015 British Society for Haematology guideline because alkaline urine promotes calcium phosphate precipitation in the tubules, and alkalinization is irrelevant once rasburicase has been given. Accepting a creatinine as high as 265 µmol/L would restart cytotoxic therapy in a patient with substantial residual renal impairment, in whom impaired clearance of both metabolites and chemotherapy raises the risk of recurrent and more severe tumor lysis. Prevention for subsequent cycles rests on vigorous intravenous hydration to maintain high urine output, rasburicase for high-risk disease such as Burkitt lymphoma, allopurinol for intermediate risk, and measurement of potassium, phosphate, calcium, uric acid and creatinine every 4 to 6 hours during the first days of each cycle. Rasburicase is contraindicated in glucose-6-phosphate dehydrogenase deficiency because it generates hydrogen peroxide and can precipitate severe hemolysis and methemoglobinemia.

Tumor Lysis Syndrome Resolution Criteria

Explanation

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