Tumor lysis syndrome

Background
  • Typically occurs within 1 to 5 days of initiation of chemotherapy
  • Associated with treatment of acute leukemia, 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
    • 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[1]

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

Differential Diagnosis

Oncologic Emergencies

Evaluation

Work Up
  • CBC
  • Chemistry
    • Elevated Cr
  • Calcium, phosphate
  • Uric Acid
  • LDH - >2-3 fold increase stratifies into higher TLS risk[2]
  • Urinalysis
  • ECG
Avoid IV contrast

Management

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

Hypocalcemia Treatment
  • ≤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
  • Treat the underlying cause
  • Restrict calcium phosphate intake
  • IV Normal Saline (if normal renal fx)
  • Acetazolamide (500mg IV q6hr) - if normal renal function
  • Phosphate Binder - Aluminum hydroxide (50-150mg/kg PO q4-6h) - limited effect
  • Dialysis if refractory
  • Consider sevelamer 800-1600mg PO tid to avoid side effects of aluminum toxicity and hypercalcemia from aluminum hydroxide treatment

Hyperuricemia Treatment
  • ≥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 Treatment
  • 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
  1. Cairo MS and Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br. J. Haematol. 2004; 127(1):3–11.
  2. Held-Warmkessel J. Preventing & Managing Tumor Lysis Syndrome. Oncology Times: 25 April 2010 - Volume 32 - Issue 8 - pp 1-7
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