Question 8

College Answer

a)

Definition 
Tumor lysis syndrome (TLS) is an oncological emergency that is caused by massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation

b)

Risk factors

• Tumour-related factors: 
  • High tumour cell proliferation rate or large tumour burden
  • Chemo sensitivity of the malignancy 
  • Transformation to acute leukemia
• Patient factors: 
  • Pre-treatment hyperuricemia or hyperphosphatemia
  • A pre-existing reduction in renal function
  • Volume depletion
  • Surgery/Stress
  • Steroid treatment

c)

• Ongoing Intensive monitoring of electrolyte (K, calcium, phosphate, uric acid, urea creatinine) and fluid status important as part of both prevention and treatment
  • Justification - significant changes in electrolytes expected - hyperkalemia, hypocalcamia and hyperphosphataemia and early identification of onset of TLS.

Prevention

• Hydration to achieve urine output of at least 1 – 1.5 ml/kg (or 80 to 100 mL/m2) per hour.
  • Justification: To minimize the chance of uric acid precipitation in the renal tubules.
• Avoid potassium and calcium containing fluids and medications
  • Justification: To minimize risk of hyperkalemia and calcium phosphate deposits
• Allopurinol in doses ranging from 300 to 600 mg/day
  • Justification: To decrease uric acid formation by blocking xanthine oxidase enzyme
• Rasburicase: this is recombinant urate oxidase enzyme that converts uric acid to allantoin (5-10 times more soluble than uric acid).
  • Justification: Conversion of uric acid to allantoin makes it more soluble. Rasburicase is particularly useful in patients with pre-existing hyperuricemia.
• Alkalinization of urine eg with ural – not a common strategy
  • Justification: To convert uric acid to a more soluble urate salt, thereby diminishing the likelihood of uric acid precipitation in the tubules. However, there are no data demonstrating the efficacy of this approach.

Treatment

1. • Repeated dose of rasburicase Justification as before
   • Consideration of fluids + diuretic therapy Justification as before
   • Specific management of hyperkalemia, hypocalcamia and hyperphosphataemia Justification – avoid adverse effects and maintain normal physiology
   • Haemodialysis, for standard indications; severe electrolyte abnormalities, oliguria, fluid overload, acidosis.
     • Justification: Removes metabolites accumulated as a result of renal failure and also lowers uric acid levels very effectively

Discussion

Tumour lysis syndrome is a metabolic disorder characterized by hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia brought about by rapid tumor cell turnover. A good NEJM review article is available for the time-rich exam candidate. The current classification system demands at least two of the abovementioned electolyte abnormalities 2-7 days after the commencement of cancer therapy.

The same NEJM article contains within it Table 2, which lists the following risk factors:

• Large amount of tumour mass
• Organ infiltration by tumour
• Bone marrow involvement
• Pre-existing renal disease
• High mittic tumour activity
• The tumour's high sensivity to the cancer therapy
• High intensity of cancer therapy
• Dehydration
• Acidic urine
• Nephrotoxin exposure
• Wanton and unchecked potassium and phosphate replacement
• Barriers to the clearance of uric acid
• Pre-existing gout

Though it is described by the college as an oncological emergency, it could be pointed out that haematological malignancies are much more likely to cause tumour lysis syndrome, and it is less well known among solid tumours. This could be because of the increased vascular exposure of the haematological malignancy as compared to the relatively walled-off solid tumours. Mirrakhimov et al (2014) also suggest that the haematological malignancies are at the same time more aggressive and therefore more sensitive to chemotherapy, i.e. a larger proportion of the maligant cells will die with the first act of oncological chemoterrorism

Prevention and treatment are well covered by the college answer.

In brief summary:

Preventative measures:

• Adequate hydration
• Electrolyte monitoring
• Intelligent electrolyte replacement
• Allopurinol
• Rasburicase
• Alkalinisation of urine

Management strategies:

• Rasburicase
• Forced diuresis
• Electrolyte correction
• Hemodialysis

Tiu, Ramon V., et al. "Tumor lysis syndrome." Seminars in thrombosis and hemostasis. Vol. 33. No. 4. New York: Stratton Intercontinental Medical Book Corporation, c1974-, 2007.

Howard, Scott C., Deborah P. Jones, and Ching-Hon Pui. "The tumor lysis syndrome." New England Journal of Medicine 364.19 (2011): 1844-1854.

Cairo, Mitchell S., and Michael Bishop. "Tumour lysis syndrome: new therapeutic strategies and classification." British journal of haematology 127.1 (2004): 3-11.

Mirrakhimov, Aibek E., et al. "Tumor lysis syndrome in solid tumors: an up to date review of the literature." Rare tumors 6.2 (2014): 68-76.