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Tumor Lysis Syndrome

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Tumor Lysis Syndrome

  • Definitions
  1. Tumor Lysis Syndrome
    1. Acute tumor cell lysis post-Chemotherapy or radiation for tumor debulking
    2. Less commonly, tumor lysis may occur spontaneously with inflammatory cancers
  • Pathophysiology
  1. Massive tumor lysis releases breakdown products
    1. Uric Acid (Hyperuricemia)
    2. Phosphate (Hyperphosphatemia)
    3. Calcium (Hypocalcemia)
    4. Potassium (Hyperkalemia)
  2. Tumor breakdown products overwhelm excretion mechanism
    1. Acute Renal Failure (secondary to Hyperuricemia and Calcium Phosphate crystallization)
  • Risk Factors
  1. Renal Insufficiency
  2. Hematologic Malignancy (esp. Acute Leukemia, high grade Lymphoma)
    1. Less commonly, may occur with solid tumors
  • Causes
  • Most common associated tumors
  1. Chemotherapy induction (within first 5-7 days)
    1. Less commonly, Radiation Therapy and biologic agents may also cause tumor lysis
  2. Acute presentation of undiagnosed rapidly growing tumor
    1. Acute Lymphocytic Leukemia
    2. Lymphoma
    3. Inflammatory Breast Cancer with high rate of proliferation
  1. General symptoms
    1. Nausea or Vomiting
    2. Diarrhea
    3. Lethargy
  2. Cardiac findings
    1. Congestive Heart Failure
    2. Dysrhythmia
    3. Syncope
  3. Neurologic findings
    1. Seizures
    2. Muscle cramps
    3. Tetany
  • Diagnostics
  • Diagnosis
  • Cairo-Bishop Definition
  1. Criteria: Two present in one 24 hour period (3 days before of 7 days after Chemotherapy initiation)
    1. Serum Calcium <=7 mg/dl or 25% decrease from baseline
    2. Serum Phosphorus >=4.5 mg/dl in adults (>6.5 mg/dl children) or 25% increase from baseline
    3. Serum Potassium >=6 mEq/L or 25% increase from baseline
    4. Uric Acid >=8 mg/dl or 25% increase from baseline
  2. Interpretation: Clinical Tumor Lysis Syndrome
    1. Two lab criteria present AND
    2. One of the following
      1. Cardiac arrhythmia or sudden death
      2. Serum Creatinine >= 1.5 times upper limit of normal for age
      3. Seizure Disorder
  3. Modifications
    1. Some include symptomatic Hypocalcemia alone as full diagnostic criteria for tumor lysis
    2. Other Acute Kidney Injury definitions may be substituted for "Serum Creatinine >1.5 times normal"
  4. References
    1. Cairo (2004) Br J Haematol 127(1):3-11 [PubMed]
  • Management
  1. Continuous cardiac monitoring
  2. Hospitalization to intensive care unit at a facility where Hemodialysis and inpatient oncology are available
  3. Consult oncology
  4. Aggressive Intravenous Fluid hydration
    1. Goal Urine Output: 100 ml/hour
  5. Monitor elecrolytes every 6 hours
    1. Serum electrolytes (Serum Potassium, Renal Function tests, Serum Calcium, Serum Phosphate, serum Uric Acid)
  6. Manage electrolyte abnormalities
    1. See Hyperkalemia Management
    2. See Hypocalcemia
    3. See Hyperuricemia
    4. See Hyperphosphatemia
    5. See Acute Renal Failure
  7. Hyperuricemia management
    1. Rasburicase (Elitek)
      1. Dose: 0.2 mg/kg in 50 ml Normal Saline over 30 minutes daily for 5-7 days
      2. Preferred in moderate to severe tumor lysis
      3. Recombinant form of urate oxidase (uricase) that converts Uric Acid to allantoin
      4. Allantoin is inactive, much more soluble than Uric Acid, and much more easily renally excreted
      5. Contraindicated in G6PD Deficiency (screen high risk populations)
    2. Allopurinol
      1. Blocks nucleic acid metabolism to Uric Acid
      2. Reduces future Uric Acid production
      3. Does NOT affect Uric Acid already produced
        1. Avoid in ill patients (use rasburicase)
  8. Hyperphosphatemia management
    1. Phosphate Binders (e.g. aluminum hydroxide)
    2. Hemodialysis
  9. Hyperkalemia Management
    1. See Hyperkalemia
  10. Hypocalcemia management
    1. Hypocalcemia is secondary to Hyperphosphatemia
    2. Do not start Calcium Replacement unless Hyperphosphatemia has corrected
      1. Risk of increased Calcium Phosphate crystals and worsening Acute Renal Failure
      2. Exceptions (in which cases calcium administration is indicated
        1. Hypocalcemia related complications (e.g. Seizures, CHF)
        2. Hyperkemia related EKG changes
  11. Alkalinize urine in not recommended in most cases
    1. Not routinely recommended
  12. Hemodialysis
    1. See Hemodialysis for indications
  • Prevention
  1. Anticipate Tumor Lysis Syndrome
    1. Pretreatment with Intravenous hydration and maintain adequate Urine Output
    2. Pretreatment with Allopurinol to reduce baseline serum Uric Acid levels
    3. Pretreatment - limit intake of Potassium and phosphorus (3 days before and 7 days after initiation)
  • References
  1. Aurora and Herbert in Majoewsky (2013) EM:Rap 13(10): 1-4
  2. Shelby (2015) Crit Dec Emerg Med 29(6): 2-8
  3. Higdon (2006) Am Fam Physician 74:1873-80 [PubMed]
  4. Higdon (2018) Am Fam Physician 97(11):741-8 [PubMed]
  5. Zuckerman (2012) Blood 120(10): 1993-2002 [PubMed]