Tumor Lysis Syndrome (TLS)

Pathophysiology

• TLS results from rapid destruction of malignant cells (often after chemotherapy, steroids, or even spontaneously in highly proliferative tumors).
• Release of intracellular contents → metabolic derangements:
  • Hyperkalemia → arrhythmias, sudden death
  • Hyperphosphatemia → binds calcium → hypocalcemia → seizures, tetany, QT prolongation
  • Hyperurecemia → crystal nephropathy, acute kidney injury
  • Hypocalcemia (secondary to phosphate) → neuromuscular and cardiac complications

Risk Stratification (pharmacist role: guide prophylaxis)

• High Risk: Burkitt lymphoma, T-ALL, WBC >100 × 10⁹/L, bulky disease, LDH >2× ULN, baseline renal dysfunction.
• Intermediate Risk: DLBCL, AML with WBC 25–100 × 10⁹/L, other aggressive lymphomas.
• Low Risk: Indolent NHL, CLL (unless high WBC + venetoclax), most solid tumors.

• Laboratory TLS (LTLS): The presence of two or more metabolic abnormalities occurring within three days before or seven days after the initiation of therapy
• Clinical TLS (CTLS): Laboratory TLS accompanied by significant clinical symptoms, such as cardiac dysrhythmias, seizures, or a 1.5x increase in serum creatinine

Prevention (before chemo or tumor-lysis trigger)

1. Hydration (cornerstone)

• 2–3 L/m²/day IV fluids (start 24–48h before therapy).
• Goal urine output: 80–100 mL/m²/hr.
• Avoid potassium-containing fluids.
• Loop diuretics only if fluid overload.

2. Hypouricemic agents

• Allopurinol:
  • Dose: 300 mg PO daily (max 800 mg/day; adjust in renal impairment).
  • Start 24–48h pre-chemo.
  • Prevents new uric acid but does not reduce existing uric acid.
  • Watch for xanthine nephropathy and drug interactions (azathioprine, 6-MP).
• Rasburicase:
  • Dose: 0.1–0.2 mg/kg IV x 1 (fixed doses 3–6 mg often used).
  • Rapidly lowers uric acid (within 4h).
  • Contraindicated in G6PD deficiency.
  • Monitor uric acid with iced, heparinized tubes (avoids ex vivo breakdown).
  • Used for high-risk or established TLS.

3. Monitoring

• Labs q6–8h in high-risk: K⁺, phosphate, calcium, uric acid, creatinine, LDH.
• Continuous ECG for K⁺ abnormalities.

Treatment of Established TLS

• Fluids: Maintain high urine output.
• Rasburicase: Drug of choice if uric acid >8 mg/dL or if clinical TLS.
• Electrolyte management:
  • Hyperkalemia → insulin/dextrose, β-agonists, binders, dialysis if refractory.
  • Hyperphosphatemia → phosphate binders, dialysis if severe.
  • Hypocalcemia → treat only if symptomatic (IV calcium can worsen Ca–PO₄ precipitation).
• Dialysis: For refractory hyperkalemia, severe hyperphosphatemia, or persistent oligo-anuric renal failure.

Practical Pharmacist Pearls

• Allopurinol is prophylactic, not therapeutic. If uric acid is already high, rasburicase is required.
• Dose adjust allopurinol in renal impairment; avoid with azathioprine/6-MP.
• One dose of rasburicase is often enough; reassess before redosing (cost-saving strategy).
• Avoid alkalinization of urine (historical practice) — increases risk of calcium phosphate precipitation.
• Always screen for G6PD deficiency before rasburicase.
• Monitor closely: pharmacists should ensure TLS labs are ordered frequently and results acted upon promptly.

Summary for the oncology pharmacist:

• Hydration + monitoring = universal cornerstone.
• Allopurinol = prophylaxis in low/intermediate risk.
• Rasburicase = treatment of established TLS or prophylaxis in high-risk.
• Pharmacist role = risk stratification, selecting correct prophylaxis, adjusting doses, recognizing drug interactions, ensuring labs/monitoring, and guiding electrolyte management.

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