What are the diagnostic criteria for tumor lysis syndrome?

Diagnostic Criteria for Tumor Lysis Syndrome

Tumor lysis syndrome is diagnosed when two or more metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, or hypocalcemia) occur within 3 days before or 7 days after starting anticancer therapy, with clinical TLS requiring these laboratory findings plus at least one clinical complication such as renal insufficiency, cardiac arrhythmia, or seizures. 1, 2

Laboratory TLS (LTLS) Criteria

Laboratory TLS requires at least 2 of the following 4 metabolic derangements: 1, 2, 3

• Hyperuricemia: Uric acid >8 mg/dL in adults (>8 mg/dL in children) 2, 3
• Hyperkalemia: Potassium ≥6 mmol/L 2, 3
• Hyperphosphatemia: Phosphate >1.62 mmol/L (>4.5 mg/dL) 2, 3
• Hypocalcemia: Corrected calcium <7 mg/dL or ionized calcium <1.12 mmol/L 3

These abnormalities must occur within the critical time window of 3 days before or 7 days after initiation of cytotoxic therapy. 1, 2

Clinical TLS (CTLS) Criteria

Clinical TLS is diagnosed when laboratory TLS is present PLUS one or more of the following clinical complications: 1, 2

Renal Insufficiency

• Serum creatinine ≥1.5 times upper normal limit OR creatinine clearance <60 mL/min 2
• The panel recommends estimating glomerular filtration rate rather than relying solely on serum creatinine, as creatinine is a poor biomarker for acute kidney damage and depends on age, hydration status, and muscle mass 4

Cardiac Arrhythmias

• Ranges from intervention not indicated (Grade I) to life-threatening arrhythmias associated with congestive heart failure, hypotension, syncope, or shock (Grade IV) 4, 2
• Continuous ECG monitoring is mandatory for all patients with hyperkalemia 3

Seizures

• Ranges from brief generalized seizures well-controlled by anticonvulsants (Grade II) to status epilepticus or intractable epilepsy (Grade IV) 4, 2

Clinical Grading System

Clinical TLS is graded from I to IV based on the highest grade of observed clinical complications: 4

• Grade I: Serum creatinine 1.5× UNL or creatinine clearance 30-45 mL/min; arrhythmia not requiring intervention; no seizures
• Grade II: Serum creatinine 1.5-3× UNL or creatinine clearance 10-30 mL/min; non-urgent arrhythmia intervention; brief controlled seizures
• Grade III: Serum creatinine 3-6× UNL or creatinine clearance 10-20 mL/min; symptomatic arrhythmia incompletely controlled; poorly controlled seizures
• Grade IV: Serum creatinine >6× UNL or creatinine clearance <10 mL/min; life-threatening arrhythmias; status epilepticus

Essential Diagnostic Workup

Before and during treatment, obtain the following laboratory parameters: 2, 3

• Baseline assessment: Uric acid, potassium, phosphate, calcium, creatinine, BUN, LDH 2
• Renal function: Creatinine clearance or estimated GFR using MDRD formula or Cockroft-Gault equation 4
• Monitoring frequency for high-risk patients: Every 12 hours for first 3 days, then every 24 hours 2
• Monitoring frequency for established TLS: Every 6 hours for first 24 hours 2

Clinical Manifestations to Recognize

Symptoms typically appear within 12-72 hours after cytoreductive therapy initiation: 3

• Gastrointestinal: Nausea, vomiting, diarrhea, anorexia 1, 3
• Cardiovascular: Edema, fluid overload, congestive heart failure, cardiac dysrhythmias, syncope 1, 3
• Neurological: Lethargy, muscle cramps, tetany, seizures 1, 3
• Renal: Hematuria, oliguria, acute renal failure 3
• Life-threatening: Sudden death from hyperkalemia-induced arrhythmias 3

Critical Pitfalls to Avoid

• Do not rely on serum creatinine alone for diagnosing renal dysfunction in TLS, as it lags behind actual kidney injury and is influenced by multiple factors. Always calculate estimated GFR. 4
• Do not miss spontaneous TLS that can occur before chemotherapy initiation, particularly in highly proliferative malignancies like Burkitt's lymphoma. 3, 5
• Recognize that mortality reaches 83% in patients who develop clinical TLS versus 24% in those without clinical complications, emphasizing the importance of early diagnosis. 2
• In solid tumors, TLS mortality approaches 35% due to delayed recognition and less aggressive prophylactic measures compared to hematologic malignancies. 4, 3