Tumor lysis syndrome

Background

• Rapid turnover of tumor cells (spontaneously, after Rx) leading to release of:
  • Potassium
  • Phosphate
  • Uric acid
• Assoc w/ ALL, Burkitt lymphoma, NHL

Cairo-Bishop Definitions

• Laboratory Tumor Lysis Syndrome
  • Abnormality in 2 or more of the following, occurring w/in 3d before or 7d after chemo

1. Uric acid ≥ 8 mg/dL or 25% increase from baseline
2. Potassium ≥ 6mEq/L or 25% increase from baseline
3. Phosphate ≥ 4.5 mg/dL or 25% increase from baseline (≥ 6.5 for children)
4. Calcium ≤ 7 mg/dL or 25% decrease from baseline

• Clinical Tumor Lysis Syndrome
  • Laboratory tumor lysis syndrome plus 1 or more of the following:

1. Cr > 1.5 times upper limit of age-adjusted reference range
2. Cardiac dysrhythmia or sudden death
3. Seizure

Etiology

1. Usually occurs within 1-5 days of starting chemotherapy or radiation for rapidly growing tumors (esp leukemia/lymphoma)
2. Can present spontaneously in certain lymphoproliferative malignancies before they are diagnosed
3. Categorized according to tumor classification (heme v. solid tumor) and relationship to antitumor rx (spontaneous v. treatment-associated)

Epidemiology

1. Most common among non-Hodgkin lymphoma (esp. Burkitt lymphoma), acute and chronic leukemia
2. Solid tumors (rare): metastatic breast CA, small cell and NSC lung CA, seminoma, invasive thymoma, metastatic medulloblastoma, Merkel cell CA, ovarian CA, rhabdomyosarcoma, metastatic melanoma, vulvar CA

Pathophysiology

1. Lysed tumor cells release nucleic acid metabolites, phosphorus and potassium into circulation
2. Nucleic acids degrade into purine metabolites which are then processed by xanthine oxidase into uric acid (excreted in urine)
3. Phosphorus binds calcium leading to hypocalcemia

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

Signs/Symptoms

1. Hyperuricemia (nausea, vomiting, lethargy, renal failure)
2. Hyperkalemia (arrythmias)
3. Hyperphosphatemia (renal failure)
4. Hypocalcemia (anorexia, cramping, tetany, confusion, seizures, V tach/torsades)
5. Acute renal failure

Work Up

1. CBC
2. Chemistry
3. Calcium, phosphate
4. Uric Acid
5. LDH
6. UA
7. ECG (hyperK, hypoCa)

Imaging

Avoid IV contrast

Management

1. Agressive hydration (goal UO 3L/24hr)
2. Urine Alkalinization
   1. NaHCO3 to urine pH >= 7.0
   2. uric acid solubility increases in alkaline environment
   3. ?Efficacy

Hypocalcemia

• ≤ 7mg/dL or 25% dec in baseline
  • Treat only if symptomatic (Ca + phos leads to incr deposition)
    • Calcium gluconate 50-200mg IV

Hyperphosphatemia

• ≥4.5 mg/dL or 25% increase; ≥ 6.5mg/dL in children
  • Aluminum hydroxide (50-150mg/kg PO q4-6h)
  • Dialysis if refractory

Hyperuricemia

• ≥8mg/dL or 25% increase
  • Allopurinol 10mg/kg/d PO q8 OR 200-400 mg/m2 IV q12; renally dosed
    • Inhibition of xanthine oxidase can last 18-30h
    • Acts slowly and only against FUTURE production of uric acid
  • Urate Oxidase Rx (eg 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

• See Hyperkalemia

Diuretics (only if euvolemic)

Dialysis (criteria)

1. K > 6mEq/L
2. Significant renal insufficiency
3. Uric Acid > 10 mg/dl
4. Symptomatic hypocalcemia
5. Serum phosphorus > 10mg/dl

Disposition

• Admission

Source

Tintinalli EM Practice March '10