What are the diagnostic criteria and management strategies for tumor lysis syndrome?

How to Diagnose Tumor Lysis Syndrome

Diagnose tumor lysis syndrome using the Cairo-Bishop criteria: laboratory TLS requires at least 2 of 4 metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) within 3 days before or 7 days after chemotherapy initiation, while clinical TLS requires laboratory TLS plus at least one clinical complication (renal failure with eGFR ≤60 mL/min, cardiac arrhythmia, or seizure). 1

Diagnostic Criteria for Laboratory TLS

Laboratory TLS is defined by the presence of at least 2 of the following 4 biochemical abnormalities: 1

• Hyperuricemia: Uric acid >7.5 mg/dL or ≥1.75 mmol/L 1
• Hyperkalemia: Potassium >6.0 mmol/L or 25% increase from baseline 1
• Hyperphosphatemia: Phosphate >4.5 mg/dL (1.45 mmol/L) in adults or age-adjusted values in children, or 25% increase from baseline 1
• Hypocalcemia: Corrected calcium <7 mg/dL (1.75 mmol/L) or 25% decrease from baseline 1

These abnormalities must occur within the timeframe of 3 days before or 7 days after initiation of cytotoxic therapy. 1

Diagnostic Criteria for Clinical TLS

Clinical TLS requires the presence of laboratory TLS PLUS at least one of the following clinical complications: 1

• Renal failure: Estimated glomerular filtration rate (eGFR) ≤60 mL/min 1
• Cardiac arrhythmia: Any documented arrhythmia on ECG or telemetry 1
• Seizure: Any witnessed or documented seizure activity 1

Clinical TLS is graded from I to IV based on the highest grade of observed clinical complications. 1

Essential Diagnostic Workup

Initial Laboratory Assessment

Obtain the following labs immediately when TLS is suspected: 1, 2

• Comprehensive metabolic panel: Including potassium, phosphate, calcium, uric acid, creatinine, BUN 1
• Lactate dehydrogenase (LDH): Elevated LDH reflects tumor burden and cell lysis 1
• Complete blood count: To assess white blood cell count and tumor burden 1

Critical Monitoring Considerations

Blood samples for uric acid measurement require special handling: 3

• Collect blood in pre-chilled tubes containing heparin 3
• Immediately immerse and maintain sample in ice water bath 3
• Assay plasma samples within 4 hours of collection 3

This is crucial because rasburicase enzymatically degrades uric acid in blood samples left at room temperature, leading to falsely low measurements. 3

Renal Function Assessment

Accurate measurement of kidney function is essential for diagnosis: 1

• Calculate eGFR using 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) 1
• Alternative Cockcroft-Gault equation: (140-age) × weight × 1.2 × (0.85 if female) / Serum creatinine 1
• Pediatric eGFR: 0.55 × length (cm) / serum creatinine (mg/dL) 1

Serum creatinine alone is a poor biomarker for acute kidney damage, so calculated eGFR is preferred. 1

Cardiac Monitoring

Obtain immediate ECG to assess for hyperkalemia-related cardiac toxicity: 4, 5

• Look for peaked T waves, flattened P waves, prolonged PR interval, and widened QRS complex 4
• These ECG changes indicate urgent treatment need regardless of absolute potassium level 4
• Continuous ECG monitoring is recommended for all hyperkalemic patients 4

Risk Stratification for TLS

High-Risk Malignancies

TLS occurs most frequently in rapidly proliferating hematologic malignancies: 1

• Highest risk: Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (B-ALL) 1
• High risk: Other B-cell non-Hodgkin's lymphomas, T-ALL 1
• Lower risk but possible: Solid tumors, particularly with high tumor burden or metastatic disease 6, 5

Tumor Burden Indicators

The following factors predict higher TLS risk: 1

• Elevated serum LDH level 1
• White blood cell count >50,000/mm³ 1
• Extensive bone marrow involvement 1
• Large tumor size or bulky disease 1

Patient-Specific Risk Factors

Comorbidities that increase TLS risk include: 1

• Elevated pre-treatment serum uric acid level 1
• Pre-existing renal damage 1
• Tumor infiltration in the kidney 1
• Obstructive uropathy 1
• Advanced age 1

Common Diagnostic Pitfalls

Spontaneous TLS

TLS can occur spontaneously without chemotherapy initiation: 6, 5

• Maintain high clinical suspicion in patients with high tumor burden even before treatment 6
• Spontaneous TLS has been reported in solid tumors including metastatic prostate adenocarcinoma 6
• Early diagnosis is critical as spontaneous TLS carries high mortality 6

Solid Tumor TLS

Do not dismiss TLS in solid tumor patients: 6, 5

• While rare compared to hematologic malignancies, TLS can occur in solid tumors 6, 5
• Solid tumor TLS is increasingly recognized with newer targeted therapies and immune checkpoint inhibitors 5
• The same diagnostic criteria apply regardless of tumor type 1, 5

Laboratory Measurement Errors

Improper sample handling leads to falsely low uric acid levels: 3

• Failure to ice samples immediately results in enzymatic degradation of uric acid 3
• This can mask the diagnosis and delay appropriate treatment 3
• Always use pre-chilled tubes and ice water bath for uric acid samples 3