Tumor Lysis Syndrome (TLS)

Symptoms

• Often asymptomatic early — detected on labs
• Nausea, vomiting, diarrhea, anorexia
• Lethargy, confusion, muscle cramps, tetany, paresthesias (hypocalcemia)
• Seizures (severe hypocalcemia or uremia)
• Palpitations, syncope, cardiac arrest (hyperkalemia)
• Decreased urine output, hematuria, flank pain

Signs / physical exam

• Chvostek and Trousseau signs (hypocalcemia)
• Cardiac arrhythmias on telemetry — peaked T waves, prolonged QRS in hyperkalemia
• Prolonged QT in hypocalcemia
• Volume overload from AKI; uremic signs

Classic findings

Patient with bulky lymphoma or hyperleukocytic leukemia who within 12-72 hours of starting chemotherapy develops oliguria, hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia.

Diagnostic criteria

Cairo-Bishop criteria — Laboratory TLS = ≥2 of the following within 3 days before or 7 days after chemotherapy initiation: - Uric acid ≥8 mg/dL or 25% increase from baseline - Potassium ≥6 mEq/L or 25% increase - Phosphate ≥4.5 mg/dL (adult) / ≥6.5 (pediatric) or 25% increase - Calcium ≤7 mg/dL or 25% decrease Clinical TLS = Laboratory TLS PLUS ≥1: creatinine ≥1.5x ULN, cardiac arrhythmia/sudden death, or seizure.

Labs

• Basic metabolic panel — potassium, calcium, phosphate, creatinine, BUN, bicarbonate
• Uric acid
• LDH (marker of cell turnover and risk)
• Magnesium, albumin (corrected calcium)
• Urinalysis — uric acid crystals, hematuria, casts
• Pre-chemotherapy labs and frequent monitoring (every 4-6 h x 24-48 h, then daily) in high-risk patients

Imaging

• Renal ultrasound if AKI and concern for obstruction or hydronephrosis
• ECG — assess hyperkalemia and hypocalcemia changes

First-line

• PREVENTION is the cornerstone — risk-stratify all patients before initiating cytotoxic therapy
• Aggressive IV hydration — isotonic crystalloid (0.9% NaCl or balanced) targeting urine output 80-100 mL/m²/h; start 24-48 h before chemo when possible
• Allopurinol (xanthine oxidase inhibitor) — oral 100 mg/m² q8h or IV — for low-to-intermediate risk; start 24-48 h before chemo and continue 3-7 days
• Rasburicase (recombinant urate oxidase) — preferred for high-risk patients or established hyperuricemia; 0.2 mg/kg IV daily; CONTRAINDICATED in G6PD deficiency (causes severe hemolysis and methemoglobinemia)
• Frequent electrolyte monitoring (q4-6h in high-risk patients)
• AVOID urinary alkalinization (no longer recommended — promotes calcium phosphate precipitation)
• Avoid potassium- and phosphate-containing fluids

Low-risk TLS

• Standard hydration
• Allopurinol prophylaxis if any risk factors
• Daily labs

Intermediate-risk TLS

• Vigorous hydration
• Allopurinol — increase to rasburicase if uric acid rises despite allopurinol
• Labs q8-12h initially

High-risk TLS (Burkitt, ALL with high WBC, AML hyperleukocytosis, bulky lymphoma)

• Pre-treatment rasburicase (single dose 0.15-0.2 mg/kg often sufficient)
• G6PD screening before rasburicase if possible
• ICU-level monitoring
• Continuous telemetry
• Frequent labs q4-6h
• Renal/critical care consultation; early dialysis if needed

Established TLS with AKI/severe electrolyte derangements

• Renal replacement therapy (hemodialysis or CRRT) for: refractory hyperkalemia, severe hyperphosphatemia, symptomatic hypocalcemia, volume overload, uremia, or oligo/anuria
• Treat hyperkalemia (insulin/dextrose, beta-agonists, calcium gluconate for cardiac protection, potassium binders)
• Treat symptomatic hypocalcemia (IV calcium ONLY if symptomatic — supplementing can worsen calcium phosphate precipitation)
• Phosphate binders (sevelamer) for hyperphosphatemia

Second-line / adjunct

• Renal replacement therapy as needed
• Febuxostat (alternative xanthine oxidase inhibitor) if allopurinol intolerance
• Hold subsequent chemotherapy doses until metabolic stability restored