Tumor Lysis Syndrome

Aka: Tumor Lysis Syndrome

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II. 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

III. Pathophysiology

  1. Aggressive treatment for high grade Lymphoma, Acute Lymphoblastic Leukemia or high tumor burden
    1. Results in massive tumor lysis
  2. Massive tumor lysis releases breakdown products
    1. Increased Potassium (Hyperkalemia)
      1. Most serious lab abnormality in Tumor Lysis Syndrome
    2. Decreased Calcium (Hypocalcemia)
      1. Most common Electrolyte abnormality in tumor lysis
      2. Lysed cells bind Free Calcium and Phosphorus increases
    3. Increased Phosphate (Hyperphosphatemia)
      1. Risk of Calcium Phosphate deposition in Kidneys
      2. Increased risk when sPh x sCa >70 (mg/dl)^2
    4. Increased Uric Acid (Hyperuricemia)
      1. Purine Nucleic Acids enzymatically degraded by xanthine oxidase
      2. May form crystals and result in Acute Kidney Injury
  3. Tumor breakdown products overwhelm excretion mechanism
    1. Acute Renal Failure (secondary to Hyperuricemia and Calcium Phosphate crystallization)

IV. Risk Factors

  1. Hematologic Malignancy
    1. High grade Lymphoma
    2. Acute Lymphoblastic Leukemia
  2. Solid cancers with high tumor burden (less common)
  3. Renal Insufficiency
  4. Lactate Dehydrogenase Increased

V. Causes: Most common associated tumors

  1. Aggressive 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 Lymphoblastic Leukemia
    2. High grade Lymphoma
    3. Inflammatory Breast Cancer with high rate of proliferation

VI. Findings: Presentations related Hyperkalemia, Acute Renal Failure

  1. General symptoms
    1. Nausea or Vomiting
    2. Diarrhea
    3. Lethargy
    4. Decreased Urine Output
  2. Cardiac findings
    1. Congestive Heart Failure
    2. Dysrhythmia
    3. Syncope
  3. Neurologic findings
    1. Seizures
    2. Muscle cramps and myalgias
    3. Tetany

VII. Labs: Chemistry panel

  1. Renal Function tests: Acute Renal Failure
    1. Typically due to Uric Acid and Calcium Phosphate precipitation in the renal tubule
    2. Blood Urea Nitrogen increased
    3. Serum Creatinine increased
  2. Serum bicarbonate or ABG
    1. Metabolic Acidosis
  3. Serum Phosphate
    1. Hyperphosphatemia
  4. Serum Potassium
    1. Hyperkalemia
  5. Serum Calcium
    1. Hypocalcemia
  6. Serum Uric Acid
    1. Hyperuricemia
  7. Lactate Dehydrogenase
    1. Increased Lactate Dehydrogenase in Tumor Lysis

VIII. Diagnostics

  1. Electrocardiogram (EKG)
    1. See Hyperkalemia Related EKG Changes

IX. 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]

X. 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 (Normal Saline)
    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. Hyperkalemia Management
    1. See Hyperkalemia Management
    2. Most emergent of the Electrolyte abnormalities
  8. Hyperphosphatemia management
    1. Restrict phosphate intake
    2. Phosphate Binders (e.g. aluminum hydroxide, Calcium Carbonate, Sevelamer)
    3. Hemodialysis
  9. 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
  10. 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, 10 fold more soluble than Uric Acid, and much more easily renally excreted
      5. Contraindicated in G6PD Deficiency (screen high risk populations)
      6. Dopes not prevent Renal Failure or decrease mortality
    2. Allopurinol
      1. Used preventively (prior to Chemotherapy)
      2. Blocks Nucleic Acid metabolism to Uric Acid
      3. Reduces future Uric Acid production
      4. Does NOT affect Uric Acid already produced
        1. Avoid in ill patients (use rasburicase)
  11. Alkalinizing urine in not recommended in most cases
    1. No supporting data for Urine Alkalinization with Sodium Bicarbonate
    2. Associated with renal Calcium Phosphate crystal formation
  12. Hemodialysis
    1. See Hemodialysis for indications

XI. 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)

XII. References

  1. Aurora and Herbert in Majoewsky (2013) EM:Rap 13(10): 1-4
  2. Long, Long and Koyfman (2020) Crit Dec Emerg Med 34(11): 17-24
  3. Shelby (2015) Crit Dec Emerg Med 29(6): 2-8
  4. Higdon (2006) Am Fam Physician 74:1873-80 [PubMed]
  5. Higdon (2018) Am Fam Physician 97(11):741-8 [PubMed]
  6. Zuckerman (2012) Blood 120(10): 1993-2002 [PubMed]

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