What are the diagnostic criteria and treatment for tumor lysis syndrome?

Diagnosis of Tumor Lysis Syndrome

Tumor lysis syndrome is diagnosed using the Cairo-Bishop criteria, which define laboratory TLS as the presence of at least 2 of 4 metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, or hypocalcemia) occurring within 3 days before or 7 days after chemotherapy initiation. 1, 2

Diagnostic Criteria

Laboratory TLS (LTLS)

Laboratory TLS requires at least 2 of the following 4 biochemical abnormalities occurring within the specified timeframe: 1, 2

• Hyperuricemia: Uric acid levels above normal or a 25% increase from baseline
• Hyperkalemia: Potassium levels above normal or a 25% increase from baseline
• Hyperphosphatemia: Phosphate levels above normal or a 25% increase from baseline
• Hypocalcemia: Calcium levels below normal or a 25% decrease from baseline

The Cairo-Bishop system specifically addresses shortcomings of earlier classification systems by not requiring a fixed 25% increase when baseline values are already abnormal, and by extending the diagnostic window from 3 days before to 7 days after treatment initiation rather than limiting it to 4 days post-treatment. 1

Clinical TLS (CTLS)

Clinical TLS requires the presence of laboratory TLS plus at least one of the following clinical complications: 1, 2

• Renal insufficiency: eGFR ≤60 mL/min/1.73 m² or creatinine increase >1.5 times upper limit of normal 2, 3
• Cardiac complications: Arrhythmias, ventricular tachycardia, fibrillation, or sudden cardiac death 1
• Neurological complications: Seizures, tetany, or syncope 1

Essential Diagnostic Workup

When TLS is suspected, immediately obtain: 2

• Comprehensive metabolic panel (including uric acid, potassium, phosphate, calcium, creatinine, BUN)
• Lactate dehydrogenase (LDH)
• Complete blood count
• ECG monitoring for hyperkalemic patients 1

Calculate eGFR using the MDRD formula: eGFR (mL/min/1.73 m²) = 175 × (serum creatinine [mmol/L] × 0.0113)^-1.154 × age (years)^-0.203 × (0.742 if female). 2

Clinical Manifestations to Monitor

Symptoms typically occur within 12 to 72 hours after chemotherapy initiation and may include: 1

• Gastrointestinal: Nausea, vomiting, diarrhea, anorexia
• Cardiovascular: Cardiac dysrhythmias, congestive heart failure, hypotension
• Renal: Hematuria, oliguria, fluid overload, edema
• Neurological: Lethargy, seizures, muscle cramps, tetany, syncope
• Life-threatening: Possible sudden death

Risk Stratification

TLS occurs most frequently in rapidly proliferating hematologic malignancies, with highest risk in: 1, 2

• Burkitt's lymphoma
• B-cell acute lymphoblastic leukemia (B-ALL)
• Acute myeloid leukemia (AML)
• High-grade non-Hodgkin lymphoma (NHL)

High-risk features predicting TLS development include: 1, 2

• Elevated serum LDH level
• White blood cell count >50,000/mm³
• Extensive bone marrow involvement
• Large tumor size or bulky disease
• Pre-existing elevated uric acid (≥8 mg/dL carries 11.66-fold increased risk compared to <4 mg/dL) 1
• Pre-existing renal impairment
• Tumor infiltration in the kidney or obstructive uropathy
• Advanced age

Treatment Approach

For Clinical TLS or High-Risk Laboratory TLS

Immediately initiate aggressive hydration and rasburicase for all patients with clinical TLS. 1

Hydration protocol: 1

• Start at least 48 hours before chemotherapy when possible
• Maintain urine output at least 100 mL/hour (3 mL/kg/hour in children <10 kg)
• Use central venous access for administration
• Add loop diuretics (furosemide) or mannitol if needed to maintain urine output, except in obstructive uropathy or hypovolemia

Rasburicase administration: 1, 3

• Dose: 0.15-0.2 mg/kg/day IV over 30 minutes
• Duration: Typically 5 days, though may be shortened based on response
• Contraindications: G6PD deficiency (risk of hemolysis and methemoglobinemia) 3
• Efficacy: Achieves uric acid ≤7.5 mg/dL in 87% of patients by 4 hours 3

Electrolyte Management

Hyperphosphatemia (>1.62 mmol/L): 1

• Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric)
• Mild hyperphosphatemia (<1.62 mmol/L) does not require treatment

Hypocalcemia: 1

• Asymptomatic hypocalcemia does not require treatment
• For symptomatic hypocalcemia (tetany, seizures): Calcium gluconate 50-100 mg/kg IV, repeat cautiously if needed

Hyperkalemia: 1, 4

• Mild (<6 mmol/L): Hydration, loop diuretics, sodium polystyrene 1 g/kg (oral or enema)
• Severe (≥6 mmol/L or ECG changes):
  • Calcium gluconate 50-100 mg/kg IV over 2-5 minutes to stabilize myocardial membrane
  • Rapid insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg
  • Calcium carbonate 100-200 mg/kg/dose
  • Sodium bicarbonate for acidosis correction
  • Continuous ECG monitoring required

Renal Replacement Therapy

Hemodialysis is indicated for: 1

• Severe refractory hyperkalemia
• Oliguria or anuria
• Acute renal failure unresponsive to medical management
• Severe hyperphosphatemia with symptomatic hypocalcemia

Hemodialysis provides uric acid clearance of 70-100 mL/min and reduces plasma uric acid by approximately 50% with each 6-hour treatment. 1

Critical Pitfalls to Avoid

Do not administer calcium supplementation for asymptomatic hypocalcemia in the setting of hyperphosphatemia, as this can precipitate calcium-phosphate crystal deposition in tissues and worsen renal injury. 1

Do not delay rasburicase administration in favor of allopurinol for established TLS—rasburicase is significantly more effective, achieving therapeutic uric acid levels within 4 hours compared to days with allopurinol. 3

Screen for G6PD deficiency before administering rasburicase, as it can cause life-threatening hemolysis and methemoglobinemia in deficient patients. 3

Monitor for TLS development before chemotherapy initiation, as spontaneous TLS can occur in highly proliferative tumors even without treatment. 1