How do you approach TLS?

How do you approach TLS?

Tumor Lysis Syndrome (TLS) is one of the need-to-know oncologic life-threatening emergencies. Let us dive into a quick review of what you need-to-know.


What is the pathophysiology of TLS?

Destruction of tumor cells due to

  • a high tumor cell proliferation rate / large tumor burden resulting in high cell turnover rates
  • destruction from chemotherapy (usually within 12-72 hours)

leads to the release of their intra-cellular contents resulting in:

  • hyperkalemia which leads to cardiac arrhythmias
  • hyperphosphatemia which can cause acute kidney injury
    • malignant cells contain 4x the concentration of phosphate compared to normal cells
  • hypocalcemia caused by binding with the excess phosphate
    • a calcium phosphate product (serum Ca x serum phos) > 60 mg2/dL2 predicts an increased risk of calcium phosphate precipitation in renal tubules leading to AKIs
  • hyperuricemia from the catabolism of purine nucleic acids
    • results in leads to worsening renal failure from direct uric acid nephrotoxicity and afferent arteriole vasoconstriction

Which patients are at highest risk?

  • Those with hematological malignancies such as non-hodgkin’s lymphoma (especially Burkitt’s Lymphoma) and leukemia (i.e. AML, ALL).
    • These patients can be further risk stratified based on their WBC count, LDH levels and tumor burden.
  • Generally, most solid tumors are considered low risk (rare exceptions).
  • Fluid derangements from dehydration and exposure to nephrotoxins increase the risk for TLS. 

What are key prophylactic options for TLS?

  • Monitoring and Hydration: for everyone with any level of risk of TLS
  • Allopurinol: a xanthine oxidase inhibitor that prevents formation of uric acid.
  • Rasburicase: metabolizes existing uric acid.
    • contraindicated in patients with G6PD
  • Allopurinol and Rasburicase are not given together. Selection is based on severity of TLS risk
    • Low Risk Disease: Monitoring, Hydration, ±Allopurinol
    • Int Risk Disease: Monitoring, Hydration, Allopurinol
    • High Risk Disease: Monitoring, Hydration, Rasburicase
  • Urinary alkalinization is no longer recommended as it can precipitate hyperphosphatemia.

How do you diagnose TLS?

  • The Cairo-Bishop definition provides specific labarotary criteria for making a Dx of and for grading the severity of TLS.
  • Laboratory TLS: Need 2/4 electrolyte abnormalities as listed below or a 25% increase (decrease for calcium) from the patient’s baseline within 3 days before or 7 days after instituting chemotherapy:
    • Potassium ≥ 6 mEq
    • Phosphorous ≥ 4.5 mEq
    • Uric acid ≥ 8 mEq
    • Calcium  ≤ 7 mEq
  • Clinical TLS: laboratory TLS plus one or more of the following that was not attributable to a therapeutic agent:
    • increased serum creatinine (≥1.5 times the ULN)
    • cardiac arrhythmia/sudden death
    • seizure
  • Check out this neat table on UpToDate that summarizes the Dx and severity criteria.

How do you treat TLS?

  • Maintain adequate hydration.
  • Treat underlying electrolyte abnormalities with special consideration for hypocalcemia and hyperuricemia.
    • For hypocalcemia:
      • Asymptomatic hypocalcemia: do not replete Ca due to the risk of precipitating calcium-phosphate complexes.
      • if the calcium phosphate product > 60, then avoid calcium.
    • For hyperphosphatemia: phosphate binders (Sevelamer with meals).
    • For hyperuricemia: Rasburicase metabolizes uric acid.

What are the indications for dialysis?

  • Persistent hyperkalemia despite treatment
  • Calcium-phosphate product ≥ 70
  • Hyperphosphatemia induced symptomatic hypocalcemia
  • Severe oliguria or anuria
  • Volume overload

References

  1. Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004;127(1):3–11. doi:10.1111/j.1365-2141.2004.05094.x
  2. Jones GL, Will A, Jackson GH, Webb NJ, Rule S; British Committee for Standards in Haematology. Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2015;169(5):661–671. doi:10.1111/bjh.13403
  3. Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767.

Post reviewed and edited by @udaygulati

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