What are the diagnostic criteria and management options for Tumor Lysis Syndrome (TLS)?

Tumor Lysis Syndrome Diagnostic Criteria

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, while clinical TLS requires laboratory TLS plus at least one clinical complication (renal insufficiency with eGFR ≤60 mL/min, cardiac arrhythmia, or seizure). 1, 2

Laboratory TLS (LTLS) Criteria

Laboratory TLS requires two or more of the following metabolic abnormalities within the specified timeframe 1:

Specific Laboratory Thresholds

Hyperuricemia:

• Uric acid >8 mg/dL in adults or >10 mg/dL in children 1
• OR 25% increase from baseline if recent baseline available 1

Hyperkalemia:

• Potassium ≥6.0 mmol/L 1
• OR 25% increase from baseline 1

Hyperphosphatemia:

• Phosphate ≥4.5 mg/dL (1.45 mmol/L) in adults or ≥6.5 mg/dL (2.1 mmol/L) in children 1
• OR 25% increase from baseline 1

Hypocalcemia:

• Calcium ≤7 mg/dL (1.75 mmol/L) 1
• OR 25% decrease from baseline 1

Clinical TLS (CTLS) Criteria

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

Clinical Manifestations

Renal insufficiency:

• eGFR ≤60 mL/min 1, 2
• Calculate 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, 2

Cardiac complications:

• Arrhythmias, ventricular tachycardia, fibrillation, or cardiac arrest 1
• Sudden death 1

Neurological complications:

• Seizures 1, 2
• Muscle cramps, tetany, paresthesia 1

Grading System

Laboratory TLS: Present or absent (binary classification) 1

Clinical TLS: Graded I-IV based on the maximal severity of clinical complications 1:

• Grade reflects the highest grade of observed clinical manifestations (renal failure, cardiac arrhythmia, or seizures) 1

Timing Considerations

The Cairo-Bishop criteria specifically define the temporal window as 3 days before to 7 days after initiation of cytoreductive therapy 1, 2. This addresses the limitation of earlier classification systems that only considered changes within 4 days after therapy initiation and failed to account for spontaneous TLS or pre-treatment abnormalities 1.

Additional Clinical Manifestations

Beyond the diagnostic criteria, patients may present with 1, 3:

• Nausea, vomiting, diarrhea, anorexia 1, 3
• Lethargy, edema, fluid overload 1, 3
• Hematuria, congestive heart failure 1, 3
• Syncope 1, 3

Symptoms most commonly occur 12 to 72 hours after initiation of cytoreductive therapy, though they may occur before treatment starts 1, 3.

Risk Stratification

Highest risk malignancies include 1, 2, 3:

• Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (B-ALL) 1, 2, 3
• High-grade non-Hodgkin lymphoma 1, 3
• Acute myeloid leukemia (AML) 1, 3

Key risk factors predicting TLS development 1, 2:

• Elevated LDH level 1, 2
• White blood cell count >50,000/mm³ 1, 2
• Bulky disease or large tumor size 1, 2
• Extensive bone marrow involvement 1, 2
• Pre-existing elevated uric acid level 1, 2
• Pre-existing renal impairment 1, 2
• Advanced age 1, 2

Essential Diagnostic Workup

When TLS is suspected, immediately obtain 2:

• Comprehensive metabolic panel 2
• Lactate dehydrogenase (LDH) 2
• Complete blood count 2

Monitoring frequency for at-risk patients 4, 3:

• Check uric acid, potassium, phosphorus, calcium, creatinine, and BUN every 12 hours for first 3 days 4
• Monitor vital signs, urine output, and electrolytes every 6 hours for first 24 hours 4

Common Pitfalls

The 25% change criterion does not apply to patients with pre-existing abnormal values at baseline—absolute threshold values should be used instead 1. This was a major shortcoming of earlier classification systems that the Cairo-Bishop criteria specifically addressed 1.