Tumor Lysis Syndrome

Epidemiology

  • Tumor lysis syndrome usually occurs during chemotherapy or within 1-5 days after chemotherapy
    • Rare cases have been reported where tumor lysis occurs in the setting of spontaneous necrosis of a malignancy (without chemotherapeutic treatment)
  • Tumor lysis syndromes has been reported to occur with multiple agents
    • Fludarabine
    • Gemtuzumab
    • Glucocorticoids
    • Letrozole
    • Rituximab
    • Tamoxifen

Etiology

  • Treatment of Burkitt’s Lymphoma/Other Rapidly Proliferating Lymphomas (see Lymphoma)
    • Predictors of Tumor Lysis
      • Elevated Serum LDH (which is also correlated with tumor burden): >1500 IU/L
      • Hyperuricemia (which is also correlated with tumor burden)
      • Poor Renal Function
      • High Tumor Burden
  • Treatment of Acute Lymphocytic Leukemia (ALL) (see Acute Lymphocytic Leukemia)
  • Treatment of Acute Myeloid Leukemia (AML) (see Acute Myeloid Leukemia)
  • Treatment of Chronic Lymphocytic Leukemia (see Chronic Lymphocytic Leukemia)
    • Has been reported with Fludarabine treatment (see Fludarabine)
  • Treatment of Chronic Myeloid Leukemia (see Chronic Myeloid Leukemia): occurs less commonly
  • Treatment of Solid Tumors: occurs less commonly

Physiology

  • Destruction of Large Number/Mass of Rapidly Proliferating Neoplastic Cells: increased turnover of nucleic acids -> hyperuricemia
    • Uric acid precipitation in renal tubules/medulla/collecting ducts (due to acidic local environment): may be exacerbated by dehydration and lactic acidosis

Clinical

  • Elevated Serum LDH
    • Levels >1500 IU/L -> predict development of tumor lysis syndrome in Burkitt’s lymphoma
  • Hyperuricemia (see Hyperuricemia)
    • Mechanism: increased turnover of nucleic acids from lysed cells
  • Hyperkalemia (see Hyperkalemia)
    • Mechanism: release of intracellular potassium
  • Hypocalcemia (see Hypocalcemia)
    • Mechanism: release of intracellular phosphate strores -> results in a reciprocal depression of serum calcium
  • Hyperphosphatemia (see Hyperphosphatemia)
    • Mechanism: release of intracellular phosphate strores -> results in a reciprocal depression of serum calcium
  • Lactic Metabolic Acidosis (see Metabolic Acidosis-Elevated Anion Gap and Lactic Acidosis)
  • Acute Kidney Injury (AKI) (see Acute Kidney Injury)
    • Mechanisms
      • Calcium Phosphate Deposition in Kidney
      • Hyperphosphatemia
      • Hyperuricemia with Uric Acid Crystal Deposition in Kidney
    • Diagnosis
      • Urinalysis: uric acid crystals is strong evidence for the presence of urate nephropathy
      • Urinary Uric Acid:Urinary Creatinine Ratio: >1 -> suggests urate nephropathy (while ratio <1 suggests AKI due to other causes)
    • Prognosis: excellent (once uric acid is decreased to <10 mg/dL)

Treatment

  • Monitoring
    • Follow serum chemistry q4-6hrs
  • Allopurinol (see Allopurinol)
    • May be used IV, in cases where PO therapy is not tolerated
  • IVF Hydration
  • Urine Alkalinization
    • Use D5W + 3 amps sodium bicarb per liter -> run at 250 ml/hr
    • Aim to maintain urine pH >7.0
    • May inadvertently promote urinary precipitation of calcium phosphate (which is less soluble at alkaline pH)
  • Rasburicase (Elitek) (see Rasburicase): recombinant urate oxidase -> catalyzes conversion of uric acid to allantoin (which is soluble)
    • Decreases uric acid within hours
    • Dose: 0.2 mg/kg/day
    • Indications: tumor lysis syndrome where uric acid cannot be lowered by above therapies
    • Contraindications: G6PD deficiency (as these patients will be unable to break down the hydrogen peroxide end product of the urate oxidase reaction
    • Adverse Effects: bronchospasm, hypoxemia, hypotension
  • Hemodialysis: may be required in some cases

References

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