Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is the development of electrolyte and metabolic disturbances that may occur following the treatment of cancer and can result in life-threatening complications if not managed appropriately. Tumor lysis syndrome is caused by the sudden, rapid death of cells, particularly cancer cells in patients with leukemia or lymphoma, in response to cancer therapies. Tumor lysis syndrome may occur spontaneously, although the occurrence of this is rare. When cancer cells are killed by therapy, they may spill their inner (intracellular) contents, which accumulate in the body faster than can be eliminated. These intracellular contents cause the metabolic and electrolyte disturbances that result in TLS.

Some patients feel no symptoms of TLS in its early stages, but have abnormal laboratory results indicative of its progression. Laboratory results will show high potassium, uric acid, and phosphorous levels and low calcium levels in the blood. Some patients with TLS may have initial symptoms including nausea and vomiting, shortness of breath, an irregular heartbeat, clouding of urine, lethargy, and/or joint discomfort. If TLS is untreated, its progression may cause acute kidney failure, cardiac arrhythmias, seizures, loss of muscle control, and death. Fortunately, TLS is a preventable and treatable condition, particularly in its early stages.

Patients at a high risk of developing TLS typically have acute leukemia or lymphoma that is very responsive to chemotherapy. Patients with pre-existing kidney dysfunction are also at an increased risk of developing TLS. Patients who are considered to be at risk of developing TLS are typically treated with preventive measures before and during their treatment for cancer. Intravenous hydration, medications including allopurinol or Elitek® (rasburicase), and alkalinization of the urine with sodium bicarbonate are typically used. Once TLS has actually developed, a patient is also treated for the specific medical abnormality that is present, which typically includes one of the following:

Hyperuricemia - Hyperuricemia refers to excess uric acid in the blood. Uric acid is the end product of the degradation or breakdown of certain proteins and is normally eliminated through the urine. When excess uric acid is present, it is converted to crystals formed of sodium urate. These crystals may deposit in the tiny tubes that are part of the kidney thus blocking them and causing acute kidney damage, which can ultimately lead to kidney failure.

Treatment for hyperuricemia may include intravenous administration of fluids, diuretics to promote excretion of uric acid in the urine, an agent such as rasburicase or allopurinol to reduce the formation of uric acid and the alkalinization of urine.

A clinical trial conducted to compare rasburicase with allopurinol in children with lymphoma or leukemia who were at a high risk for developing TLS demonstrated that uric acid levels in the blood were significantly lower in patients treated with rasburicase than in patients treated with allopurinol. Four hours after treatment, uric acid levels were decreased by 86 percent in patients treated with rasburicase compared with only 12 percent in patients treated with allopurinol. Furthermore, levels of the metabolic compound creatinine, indicating kidney malfunction, improved during the 4 days of treatment with rasburicase and actually worsened during treatment with allopurinol.

Hyperkalemia - Hyperkalemia refers to excess potassium in the blood. Elevated levels of potassium can cause irregular cardiac (heart) rhythms and neuromuscular dysfunction.

Treatment for hyperkalemia may include calcium administered intravenously to counterbalance the effects of elevated levels of potassium on the heart; dextrose (sugar) and insulin so that potassium is taken into cells, which reduces levels in the blood; agents to bind to potassium and promote elimination through the bowel; diuretics to promote potassium excretion in the urine; and sodium bicarbonate or an alkalizing agent to help neutralize the effects of hyperkalemia.

Hyperphosphatemia - Hyperphosphatemia refers to the presence of excess phosphates in the blood. Elevated levels of phosphates can cause low levels of calcium in the blood, or hypocalcemia. Complexes of phosphates and calcium can form and deposit in tiny tubes of the kidneys, which can ultimately lead to kidney failure.

Treatment for hyperphosphatemia may include agents that bind to phosphates and promote elimination through the bowel so that they do not have an effect on the body. Diuretics may also be used to promote excretion of phosphates through the urine. In addition, dietary intake of phosphates should be restricted or eliminated.

Hypocalcemia - Low levels of calcium in the blood may result in severe cardiovascular effects and neurologic dysfunction (i.e., seizures, hallucinations, and numbness).

Treatment for hypocalcemia may include the intravenous administration of some form of calcium and a diuretic to promote excretion of phosphates in urine.

Before starting treatment for cancer, patients should discuss their risk of developing TLS with their physician, as well as early warning signs that may indicate the onset of TLS.