Tumor lysis syndrome

Background

• Associated with treatment of ALL, Burkitt lymphoma, NHL
  • Rarely observed in solid tumors or without prior therapy
• Rapid turnover of tumor cells (spontaneously or after treatment) leading to release of:
  • Potassium
  • Phosphate
    • Binds Ca causing hypocalcemia
  • Uric acid (converted from nucleic acids)

Risk Factors

• High cell proliferation rate
• Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
• Extensive BM involvement
• Tumor infiltration of the kidney

Cairo-Bishop Definition

Laboratory Tumor Lysis Syndrome

• Abnormality in 2 or more of the following, occurring within 3d before or 7d after chemo:
  • Uric acid ≥ 8mg/dL or 25% increase from baseline
  • Potassium ≥ 6mEq/L or 25% increase from baseline
  • Phosphate ≥ 4.5mg/dL or 25% increase from baseline (≥ 6.5 for children)
  • Calcium ≤ 7mg/dL or 25% decrease from baseline

Clinical Tumor Lysis Syndrome

• Laboratory tumor lysis syndrome plus 1 or more of the following:
  • Creatinine > 1.5 times upper limit of age-adjusted reference range
  • Cardiac dysrhythmia or sudden death
  • Seizure

Clinical Features

• Hyperuricemia
  • Nausea/vomiting, lethargy, renal failure
• Hyperkalemia
  • Most immediate life-threatening element (due to dysrrhythmias)
• Hyperphosphatemia
  • May combine with Ca to precipiate in renal tubules
• Hypocalcemia
  • Anorexia, cramping, tetany, confusion, seizures, V-tach/torsades
• Acute Renal Failure
  • Most common cause of morbidity
  • Usually results from uric acid precipitation within renal tubules

Differential Diagnosis

Oncologic Emergencies

Related to Local Tumor Effects

• Malignant airway obstruction
• Bone metastases and pathologic fractures
• Malignant spinal cord compression
• Malignant Pericardial Effusion and Tamponade
• Superior vena cava syndrome

Related to Biochemical Derangement

• Hypercalcemia of malignancy
• Hyponatremia due to SIADH
• Adrenal insufficiency
• Tumor lysis syndrome
• Carcinoid syndrome

Related to Hematologic Derangement

• Neutropenic fever
  • Neutropenic enterocolitis (typhlitis)
• Leukostasis and hyperleukocytosis
• Hyperviscosity syndrome
• Thromboembolism

Related to Therapy

• Chemotherapy-induced nausea and vomiting
• Chemotherapeutic drug extravasation
• Differentiation syndrome (retinoic acid syndrome) in APML
• Stem cell transplant complications

Evaluation

Work Up

• CBC
• Chemistry
  • Elevated Cr
• Calcium, phosphate
• Uric Acid
• LDH - >2-3 fold increase stratifies into higher TLS risk
• Urinalysis
• ECG
  • Hyperkalemia, hypocalcemia

Avoid IV contrast

Management

Agressive hydration - Goal urine output is 3L in 24hr

Hypocalcemia

• ≤7 or 25% decrease in baseline
  • Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition), such as widened QRS or ventricular arrhythmias
  • Calcium gluconate 50-200mg IV

Hyperphosphatemia treatment

1. Treat the underlying cause
2. Restrict calcium phosphate intake
3. IV Normal Saline (if normal renal fx)
4. Acetazolamide (500mg IV q6hr) - if normal renal function
5. Phosphate Binder - Aluminum hydroxide (50-150mg/kg PO q4-6h) - limited effect
6. Dialysis if refractory

• Consider sevelamer 800-1600mg PO tid to avoid side effects of aluminum toxicity and hypercalcemia from aluminum hydroxide treatment

Hyperuricemia

• ≥8 or 25% increase
  • Allopurinol
    • Acts slowly; only helpful for preventing future production of uric acid
    • 10mg/kg/d PO q8 OR 200-400mg/m2 IV q12; renally dosed
    • Inhibition of xanthine oxidase can last 18-30h
  • Urate Oxidase
    • Rasburicase 0.05-0.2mg/kg IV
    • Can be used for BOTH prevention and treatment
    • Uric acid final product of purine metabolism
      • Urate oxidase converts uric acid to allantoin (5-10x more soluble)

Hyperkalemia

• Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
  • Giving Ca leads to increased Ca/phos deposition which leads to renal failure
• See Hyperkalemia for treatment options

Dialysis (Criteria)

• Potassium >6
• Significant renal insufficiency (Creatinine >10)
• Uric Acid >10
• Symptomatic hypocalcemia
• Serum phosphorus >10
• Volume overload

Disposition

• Admit (often to ICU)

References

Authors

Ross Donaldson