Tumor lysis syndrome

Background

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

Risk Factors

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

Cairo-Bishop Definition

Laboratory Tumor Lysis Syndrome

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

Clinical Tumor Lysis Syndrome

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

Clinical Features

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

Work Up

1. CBC
2. Chemistry
3. Calcium, phosphate
4. Uric Acid
5. LDH
6. UA
7. ECG
   • Hyperkalemia, hypocalcemia

Imaging

• Avoid IV contrast

Treatment

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

Hypocalcemia

• ≤7 or 25% dec 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

• ≥4.5 or 25% increase; ≥ 6.5mg/dL in children
  • IV insulin & glucose
  • Phosphate Binder - Aluminum hydroxide (50-150mg/kg PO q4-6h) - limited effect
  • Dialysis if refractory

Hyperuricemia

• ≥8 or 25% increase
  • Allopurinol
    • Acts slowly; only helpful for preventing future production of uric acid
    • 10mg/kg/d PO q8 OR 200-400 mg/m2 IV q12; renally dosed
    • Inhibition of xanthine oxidase can last 18-30h
  • Urate Oxidase Rx
    • 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)

1. Potassium >6
2. Significant renal insufficiency (Cr >10)
3. Uric Acid >10
4. Symptomatic hypocalcemia
5. Serum phosphorus >10
6. Volume overload

Disposition

• Admit (often to ICU)