Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is a major onco-metabolic entity in cancer patients, requiring emergency diagnosis and management. TLS can lead to severe renal impairment, cardiac arrhythmias, central nervous system toxicity, and death. Cellular death, either spontaneously or mediated by cancer treatment causes the release of potassium, phosphorus, and uric acid from rapidly dividing malignant cells into the bloodstream. Serum calcium levels decrease in patients with TLS because of its binding to phosphorus. Certain conditions are associated with high risk of TLS (hyperleukocytosis, bulky malignancies).  Every cancer patient should be assessed for the risk of TLS. Measures of prevention and treatment are based upon hyperhydration, diuretics when needed and the use of uric acid lowering agents according to the risk, with strict clinical and laboratory monitorization.

Clinical manifestations

Stratification of risk & treatment guidelines

Diagnosis of clinical and laboratory tumor lysis

Laboratory TLS (LTLS)

The presence of two or more abnormal serum values at presentation (i.e., uric acid ≥8 mg/dl, potassium ≥6 mg/dl, phosphate ≥ 2.1 mmol/l, calcium ≤1.75 mmol/l, creatinine > normal).

Clinical TLS (CTLS)

Presence of LTLS and one or more of the following clinical complications:

• renal insufficiency
• cardiac arrhythmias
• seizures
• sudden death.

Management

Hydration

• Hydration at a rate of > 2 L/m²/day should start 24 h before chemotherapy.
• Urine output goal of 3 ml/kg/h should be maintained. Diuretics may be needed to maintain this urine output.

Allopurinol

• A xanthine analog which blocks conversion of xanthine and hypoxanthine to uric acid; works as a competitive inhibitor of xanthine oxidase.
• Slow reduction in uric acid levels.
• Decreased risk of uric acid crystallization in kidney tubules.
• Adverse effects include hypersensitivity reaction and a buildup of xanthine and hypoxanthine, which may lead to renal insufficiency as well.
• Dose: 10 mg/kg/day orally divided into 3-4 doses.

Rasburicase

• Rasburicase, recombinant urate oxidase, converts uric acid into allantoin, a five to ten times more soluble compound, in an extremely effective manner.
• Assess patient’s G6PD status or risk of having G6PD, as may cause methemoglobinemia or severe hemolytic anemia.
• May require reinitiating allopurinol several days after rasburicase.
• Dose: 0.2 mg/kg IV once daily, can be repeated for 2-5 days.

Treatment of electrolytes derangements due to TLS

Indication for dialysis

• Presence of hyperphosphatemia (6 mg/dl) and hypercalcemia which promotes deposition in renal interstitium and tubular system, exacerbating kidney damage.
• An estimated GFR less than 50%.
• Persistent hyperkalemia with QRS interval widening and/or level exceeding 6 mEq/l.
• Severe metabolic acidosis.
• Volume overload unresponsive to diuretic therapy.
• Anuria and overt uremic symptoms (i.e., encephalopathy).
• Severe symptomatic hypocalcemia.
• Hypertension (BP>150/90) and inadequate urine output at 10 h from start of treatment.
• Congestive heart failure.

References

• Cairo MS, Coiffier B, Reiter A et al (2010) Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol 149:578–586
• Philip Lanzkowsky (2022). Lanzkowsky’s Manual of Pediatric Hematology and Oncology. 7^th edition. London, UK: Elsevier
• Hochberg, J., Cairo, M.S., 2008. Rasburicase: future directions in tumor lysis management. Expert Opinion on Biological Therapy 8 (10), 1595_1604.
• Howard, S.C., Jones, D.P., Pui, C.H., 2011. The tumor lysis syndrome. N. Engl. J. Med. 364 (19), 1844_1854.
• F. Perry Wilson, Jeffrey S. Onco-Nephrology: Tumor Lysis Syndrome. CJASN October 2012, 7 (10) 1730-1739