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Prevention of Tumor Lysis Syndrome


Medical editor Harald Holte MD
Oncologist
Oslo University Hospital

General

Tumor lysis syndrome is a life-threatening complication in cancers where rapid cell loss is caused when treatment is initiated.

In tumor lysis syndrome, there is a rapid decrease of cells in a matter of hours/days causing depletion of intracellular substances into extracellular space. This causes an increased serum concentration of calcium, phosphate, magnesium, urine substances, and uric acid.  

Uric acid can lead to precipitation of uric acid crystals in the renal tubules and lead to reduction of renal function. Renal failure is worsened by the binding of phosphate ions with calcium ions creating calcium phosphate crystals which also precipitate in the tubules. When calcium phosphate is > 8-10 mmol/l, the risk of precipitation of crystals in the kidneys and other tissue, increases.  

Hyperkalemia from release of intracellular potassium is the greatest acute threat to the patient. Levels > 7 mmol/l increases the risk for cardiac arrhythmia and cardiac arrest. 

Tumor lysis syndrome is observed in association with the first course of chemotherapy, start of radiation therapy, or steroid treatment.

Patients who are disposed for developing tymor lysis syndrome have:

  • a relatively large tumor mass with high cell proliferation
  • elevated leukocyte count (leukemized blood profile)
  • elevated LDH
  • elevated uric acid
  • reduced renal function 

The patient`s well being is often already influenced by the disease. Therefore, the degree of electrolyte disturbance contributes to complicating the patient's progress. 

The prognosis is good with adequate prophylaxis and timely treatment.

Indication

  • Acute leukemia, lymphoblastic lymphoma, Burkitt's lymphoma (often observed)
  • Other aggressive B- and T-cell lymphomas and indolent lymphomas with massive leukemization treated with monoclonal antibodies (less frequent) 
  • Solid tumors such as small cell lung cancer, medulloblastoma, testical cancer, and advanced breast cancer (rare) 

Goal

  • Prevention of tumor lysis syndrome

Definitions

Tymor lysis is the disintegration of tumor cells, either spontaneously or due to different forms of tumor-directed treatment.

Preparation

  • Sufficient information about the risk of developing tumor lysis syndrome.
  • Start prophylaxis for tumor lysis syndrome as soon as possible, preferably 1-2 days after starting chemotherapy. 

Implementation

Forced hydration is important.

  • Intravenous fluid for adults: 3000-8000 ml NaCl/24 hours. For children, 3000-5000 Salidex® ml/m2/day, depending on the amount of expected tumor disintegration.   
  • Administer allopurinol tablets.
  • If uric acid and creatinine values are higher than expected, rasburicase is administered intravenously, which degrades uric acid rapidly, instead of allopurinol. 
  • Ensure control of fluid accounting.
  • Observe that the hourly diuresis is over 250 ml/hour for adults. Furosemide 20 mg can be given for normal renal function for every 1000 ml of fluid administered. For reduced renal function, it may be necessary to give significantly higher doses. For children, furosemide is administered for insufficient diuresis. Hourly diuresis should be 100-250 ml/hour. 
  • Alkalization of urine is somewhat controversial, but of importance if uric acid is elevated and before and during administration of high dose methotrexate i.v.: for adults, sodium bicarbonate tablets (1-2 g x 3-5 per day) are administered. If there is a significant risk for tumor lysis, or if the patient cannot take tablets, NaHCO3 is administered intravenously (about 160 mmol/24 hours). Dosing depends on the acid-base status. For children, 40 mmol NaHCO3  per 1000 ml is added and possibly KCl additions to the hydration fluid, based on blood test results.
  • Monitoring urine should occur with pH measurements every 4 hours. The pH should be > 7.0.
  • Weighing the patient twice daily is also a method of assessing the fluid balance. 
  • Administer electrolyte supplements as needed.

When the risk of developing tumor lysis is significant after starting treatment, values for Na, K, Cl, Ca, Mg, P, creatinine, uric acid and urine substances in the blood should be checked 2 or more times daily.  

For fully developed tumor lysis syndrome, it may be necessary to repeat tests 3-5 times a day. For greater electrolyte disturbances, a venous acid-base status should also be taken.

For large electrolyte disturbances such as hyperkalemia > 7mmol/l and/or serious hypocalcemia and weakened renal function, the patient should be transferred to the intensive division. A nephrologist should be contacted for emergency help in case of dialysis.


Follow-up Care

Tumor lysis tests are checked 2-4 times in the first days after starting treatment. If the patient has not developed tumor lysis syndrome in the next 2-4 days, the patient may continue the work-up/cancer treatment or possibly return home.

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