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 (e.g. Burkitt Lymphoma)
    2. Aggressive Leukemia (e.g. Acute Lymphoblastic Leukemia)
  2. Solid cancers with high tumor burden (less common)
  3. Renal Insufficiency
  4. Lactate Dehydrogenase Increased

V. Risk Factors: Childhood risks for Tumor Lysis Syndrome

  1. Low risk level for TLS
    1. ALL with WBC <50,000/mm3
    2. AML with WBC <10,000/mm3
  2. Moderate risk level for TLS
    1. Diffuse large B Cell Lymphoma
    2. ALL with WBC 50,000 to 100,000/mm3
    3. AML with WBC 10,000 to 50,000/mm3
    4. Other malignancy with rapid proliferation and response to therapy
    5. Uric Acid level <7.5 mg/dl
  3. High risk level for TLS
    1. Burkitt Lymphoma
    2. ALL with WBC >100,000/mm3
    3. AML with WBC >50,000/mm3
    4. Uric Acid level >=7.5 mg/dl
    5. Renal Injury (Dehydration, acidosis, acidic urine)

VI. Causes: Most common associated tumors

  1. Aggressive Chemotherapy induction (within first 5-7 days, esp. first 2-3 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

VII. 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

VIII. 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
  8. Other labs
    1. Complete Blood Count with Platelets and differential
    2. Urinalysis

IX. Diagnostics

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

X. Diagnosis: Cairo-Bishop Definition

  1. Criteria: Two present in one 24 hour period (range: 3 days before or 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]

XI. Management

  1. Goals of Care
    1. Prevent Acute Kidney Injury (esp. related to Uric Acid crystallization within renal tubules)
    2. Manage Electrolyte complications (e.g. Hyperkalemia, Hyperphosphatemia, Hypocalcemia)
  2. General Measures
    1. Continuous cardiac monitoring
    2. Hospitalization to Intensive Care unit at a facility where Hemodialysis and inpatient oncology are available
    3. Consult oncology
  3. Aggressive Intravenous Fluid hydration with isotonic crystalloid (LR is preferred)
    1. Goal Urine Output: 100 ml/hour in adults (2-5 ml/kg/h in children)
    2. Prevent Acute Renal Failure
  4. Monitor elecrolytes every 6 hours
    1. Serum Electrolytes (Serum Potassium, Renal Function tests, Serum Calcium, Serum Phosphate, serum Uric Acid)
  5. Manage Electrolyte abnormalities
    1. See Hyperkalemia Management
    2. See Hypocalcemia
    3. See Hyperuricemia
    4. See Hyperphosphatemia
    5. See Acute Renal Failure
  6. Hyperkalemia Management
    1. See Hyperkalemia Management
    2. Most emergent of the Electrolyte abnormalities
    3. Most Hyperkalemia Management strategies may be used (except Calcium administration)
      1. Potassium shifting to intracellular with dextrose and Insulin
      2. Nebulized Albuterol
      3. Loop Diuretics
      4. Potassium binders
      5. Hemodialysis in refractory Hyperkalemia
    4. Avoid Calcium infusion UNLESS cardiovascular or neuromuscular instability (e.g. QRS Widening, Seizures)
      1. Calcium administration risks Calcium Phosphate crystal formation
      2. Risk decreases after Hyperphosphatemia is corrected (see below)
  7. Hyperphosphatemia management
    1. Restrict phosphate intake
    2. Phosphate Binders (e.g. aluminum hydroxide, Calcium Carbonate, Calcium acetate, Sevelamer)
    3. Hemodialysis in severe or refractory cases
  8. 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, Tetany, Arrhythmia)
        2. Hyperkemia related EKG changes
  9. 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 (esp. Uric Acid >12 mg/dl)
      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. Risk of bronchospasm, Hypoxemia, Hypotension
      7. Does not prevent Renal Failure or decrease mortality
    2. Allopurinol (or Febuxostat)
      1. Dose 50-100 mg/m2 orally every 8 hours
        1. Alternative: 10 mg/kg/day up to 800 mg/day divided every 8 hours
      2. Used preventively (prior to Chemotherapy) in patients at medium to high risk or TLS
      3. Blocks Nucleic Acid metabolism to Uric Acid (by inhibiting xanthine oxidase)
      4. Reduces future Uric Acid production
      5. Does NOT affect Uric Acid already produced
        1. Avoid in ill patients (use rasburicase instead)
  10. 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
  11. Hemodialysis
    1. See Hemodialysis for indications
    2. Consider in TLS with hypervolemia
    3. Consult nephrology for in severe TLS
      1. Corrects severe metabolic derangements (Hyperkalemia, Hyperphosphatemia) within 6-12 hours

XII. 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)

XIII. References

  1. Aurora and Herbert in Herbert (2013) EM:Rap 13(10): 1-4
  2. Bierowski and Nyalakonda (2025) Crit Dec Emerg Med 39(6): 4-21
  3. Collyer, Huang and Seo (2026) Crit Dec Emerg Med 40(1): 26-33
  4. Long, Long and Koyfman (2020) Crit Dec Emerg Med 34(11): 17-24
  5. Shelby (2015) Crit Dec Emerg Med 29(6): 2-8
  6. Higdon (2006) Am Fam Physician 74:1873-80 [PubMed]
  7. Higdon (2018) Am Fam Physician 97(11):741-8 [PubMed]
  8. Zuckerman (2012) Blood 120(10): 1993-2002 [PubMed]

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