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
    • 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

  • 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
  • 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

Related to Biochemical Derangement

Related to Hematologic Derangement

Related to Therapy

Evaluation

Work Up

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

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

  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