Tumor Lysis Syndrome Management

Introduction

Tumor lysis syndrome (TLS) is a life-threatening complication that requires aggressive management, including hydration, medication, and monitoring, as recommended by the European Society for Medical Oncology and the National Comprehensive Cancer Network 1, 2

Patients at high risk for developing TLS include those with hematologic malignancies with high tumor burden (such as ALL, Burkitt's lymphoma, AML), solid tumors with large tumor burden, pre-existing renal dysfunction, and elevated baseline uric acid levels, as recommended by the European Society for Medical Oncology 1
Patients should be stratified into risk categories to determine appropriate monitoring and prevention strategies, considering host and disease factors, as recommended by the National Comprehensive Cancer Network 1

Rasburicase should be administered at a dose of 0.20 mg/kg/day IV to rapidly degrade uric acid, allowing earlier administration of chemotherapy if needed, but is contraindicated in patients with G6PD deficiency, metahemoglobinemia, or other metabolic disorders that can potentially cause hemolytic anemia, as recommended by the European Society for Medical Oncology and the National Comprehensive Cancer Network 1, 2
Allopurinol should be administered orally at 100 mg/m²/dose every 8 hours (10 mg/kg/day divided every 8 hours) with a maximum of 800 mg/day, or intravenously at 200-400 mg/m²/day in 1-3 divided doses with a maximum of 600 mg/day, with renal adjustment by reducing the dose by 50% or more in patients with renal impairment, as recommended by the Journal of Clinical Oncology guidelines 2
Rasburicase rapidly converts existing uric acid to allantoin, which is 5-10 times more soluble in urine than uric acid, according to the European Hematology Association 1
Allopurinol prevents the formation of new uric acid but does not reduce existing levels, as stated by the European Society for Medical Oncology 1

The American Society of Clinical Oncology recommends a fluid volume of 2-3 L/m²/day (or 200 mL/kg/day if <10 kg) with a solution of one-quarter normal saline/5% dextrose, and a target output of 80-100 mL/m²/hour (4-6 mL/kg/hour if <10 kg) 2
Initially, withhold potassium, calcium, and phosphate from hydration fluids due to risks of hyperkalemia, hyperphosphatemia, and calcium phosphate precipitation 2
Attempt to achieve equal fluid intake and urinary output, and maintain urine-specific gravity at 1.010 2
Loop diuretics (or mannitol) may be used to maintain target urine output, except in patients with obstructive uropathy or hypovolemia, according to the Haematologica guidelines and the European Society for Medical Oncology 1

Consider renal replacement therapy if volume overload becomes unresponsive to diuretic therapy despite adequate hydration, with indications including persistent hyperkalemia, severe metabolic acidosis, and overt uremic symptoms 1
Indications for renal replacement therapy include acute renal failure, severe electrolyte disturbances unresponsive to medical treatment, refractory volume overload, excessively elevated uric acid or phosphorus levels, and severe metabolic acidosis, as per the Haematologica guidelines and the European Society for Medical Oncology 1
Hemodialysis reduces uric acid levels by approximately 50% with each 6-hour treatment, with uric acid clearance of approximately 70-100 mL/min, according to the Haematologica guidelines and the European Society for Medical Oncology 1

Hyperkalemia should be treated with hydration, loop diuretics, and sodium polystyrene, and severe cases should be treated with insulin and glucose, calcium carbonate, and sodium bicarbonate, with continuous ECG monitoring, as recommended by the European Society for Medical Oncology 1
For mild hyperkalemia (<6 mmol/L), hydration, loop diuretics, and sodium polystyrene 1 g/kg orally or by enema are recommended, as per the Haematologica guidelines 1
Hyperphosphatemia should be treated with aluminum hydroxide 50-100 mg/kg/day divided in 4 doses for mild cases (<1.62 mmol/L), as recommended by the European Society for Medical Oncology 1
Hypocalcemia should be treated with calcium gluconate 50-100 mg/kg as a single dose for symptomatic cases, but asymptomatic cases should not be treated with routine calcium replacement, as recommended by the European Society for Medical Oncology 1

Patients should be monitored closely, including vital signs, uric acid, electrolytes, and renal function, every 6 hours during the first 24 hours, and every 24 hours assess: blood cell count, serum LDH, albumin, serum osmolality, blood gases and acid-base equilibrium, electrocardiogram, and body weight, as recommended by the European Society for Medical Oncology 1

A retrospective analysis found that only 2.6% of patients receiving urate oxidase required dialysis, compared to 16% of those receiving allopurinol, as reported by the European Hematology Association 1