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