A. Definition

1. Metabolic abnormalities as a complication of cytotoxic therapy of malignant neoplasm
2. Laboratory Abnrmalities
   1. >2X increase in lactate dehydrogenase (LDH)
   2. >50% increase in phosphorus, uric acid or creatinine
   3. >30% increase in potassium
   4. >20% decrease in calcium
3. Clinical Manifestations
   1. Acute renal failure (ARF)
   2. Cardiac arrhythmias
   3. Sudden death

B. Occurrence

1. Spontaneous Syndrome
   1. Infrequent, seen with acute leukemias
   2. Also occasionally with lymphomas (rapidly growing such as Burkitt's)
2. Chemotherapy Associated
   1. Due to rapid lysis of malignant cells
   2. Mainly with acute leukemias
   3. Uncommon with non-Hodgkin's lymphoma, multiple myeloma
   4. Very uncommon with solid tumors
   5. Increasing with potent chemotherapeutic agents
3. Tamoxifen / Interferon / Radiation / Glucocorticoids
4. Patients with impaired renal function (especially oliguria / anuria) at much increased risk

C. Prevention of Tumor Lysis Syndrome

1. Allopurinol
   1. Reduces formation of uric acid; reduces risk of ARF
   2. Dose with normal renal function: 300mg qd
   3. Dose is 100mg qd for renal insufficiency
2. Hydration with alkalinization (not needed unless urine pH <6.0)
3. Monitor Electrolytes q12-24 hours
4. Correct as needed - especially hyperkalemia and hypocalcemia

D. Treatment of Syndrome

1. Prevent further uric acid formation [2]
   1. Allopurinol 150-300mg po qd
   2. Aloprim (allopurinol IV) 200mg/m2 IV
   3. Recombinant xanthine oxidase (rasburicase, Elitek®) 0.15-0.2mg/kg IV
   4. Rasburicase has more rapid onset and better efficacy than allopurinol
2. Hydration
3. Urinary Alkalinization to pH > 7: Bicarbonate 100mEq/L (2Amps per liter)
4. Postpone Chemotherapy
5. Replete Calcium with Ca Gluconate (Hypocalcemia and Hyperkalemia)
6. Hemodialysis if no response

References

1. Davidson MB, Thakkar S, Hix JK, et al. 2004. Am J Med. 116(8):541
2. Rasburicase. 2002. Med Let. 44(1143):96