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

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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

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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

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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)

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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

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References

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