Anticipate tumor lysis syndrome (TLS) in children with leukemia or lymphoma
Anticipate tumor lysis syndrome (TLS) in children with leukemia or lymphoma: Excerpt from Avoiding Common Pediatric Errors
Author:
Emily Riehm Meier, MD
What to Do - Interpret the Data
TLS is a constellation of metabolic abnormalities that usually occur within
the first 3 to 5 days of starting chemotherapy. Clinicians must be aware that
hydration alone can cause cell lysis, placing patients undergoing a diagnostic
oncologic work up at risk for TLS. In rare cases, TLS can occur spontaneously.Patientswithnon-HodgkinlymphomaandT-cellacutelymphoblastic leukemia have the highest risk of TLS due to the bulky lymphadenopathy
and leukocytosis often accompanying these diseases.
Hyperuricemia, hyperphosphatemia with associated hypocalcemia, and
hyperkalemia are the laboratory abnormalities seen in patients with TLS.
The intracellular ions potassium and phosphate are released when cells are
lysed by chemotherapy. Hyperuricemia occurs when DNA building blocks
(namely the purines, guanosine and adenosine) found within tumor cell nuclei are released and degraded to uric acid. A compensatory increase in
urinary excretion of uric acid and phosphate occurs. Depending on the size
of the tumor burden, the kidneys may be overwhelmed by the amount of
intracellular debris that needs to be excreted. Uric acid is soluble at physiologic pH, but in the acidic conditions commonly seen with a high cell
turnover rate and possible renal hypoperfusion, urate crystals can form in
the renal collecting system. Calcium phosphate deposits can also precipitate
in the renal tubules. These can lead to renal failure, placing the patient at risk
for further hyperkalemia and life-threatening cardiac arrhythmias. The best
treatment for TLS-associated renal failure is prevention. Hydration, urinary alkalinization, and inhibition of uric acid production are the standard
preventative interventions for TLS. Intravenous fluids usually run at high
flow rates (3 L/m2/day, approximately 2 times maintenance) with sodium
bicarbonate infused in a separate line, adjusting the infusion rate to maintain
the urine pH between 7 and 8. Uric acid precipitates at a urine pH of <7
and calcium/phosphate stones may form in urine with a pH >8. Urine pH
should be tested with each void, and adjustments to the rate of bicarbonate
infusion should be made accordingly.
Allopurinolistheclassicmedicationusedtopreventuricacidformation.
Allopurinol stops the conversion of xanthine (formed by purine breakdown)
to uric acid by blocking xanthine oxidase. This leads to a build up of the
byproducts xanthine and hypoxanthine. Xanthine is more likely to precipitate in the urine than uric acid, and cases of xanthine nephropathy have
been reported. In patients at high risk of TLS, recombinant urate oxidase
(rasburicase) can be used. Urate oxidase catalyses the conversion of uric acid
to allantoin, which is up to 10 times more soluble in urine than uric acid. In
high-risk patients, rasburicase dramatically drops hyperuricemia, avoiding
TLS-associated renal failure and its complications.
Suggested Readings
Keaney CM, Springate JE. Cancer and the kidney. Adolesc Med Clin. 2005;16:121–148.
Nicolin G. Emergencies and their management. Eur J Cancer. 2002;38:1365–1379.
Pui CH, Mahmoud HH, Wiley JM, et al. Recombinant urate oxidase for the prophylaxis or
treatment of hyperuricemia in patients with leukemia or lymphoma. J Clin Oncol. 2001;19:
697–704.
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Book Source Details
- Book Title: Avoiding Common Pediatric Errors
- Author(s): Anthony D Slonim MD, DrPH; Lisa Marcucci MD
- Year of Publication: 2008
- Copyright Details: Avoiding Common Pediatric Errors, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: Avoiding Common Pediatric Errors
Authors: Anthony D Slonim MD, DrPH; Lisa Marcucci MD
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7489-6
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