eMedicine Specialties > Pediatrics: General Medicine > Oncology
Tumor Lysis Syndrome
Updated: Sep 26, 2008
Introduction
Background
Tumor lysis syndrome (TLS) is a very serious and sometimes life-threatening complication of cancer therapy. It can be defined as a constellation of metabolic abnormalities that results from spontaneous or treatment-related tumor necrosis. The metabolic abnormalities observed in patients with tumor lysis syndrome include hyperkalemia, hyperuricemia, and hyperphosphatemia with secondary hypocalcemia. These can lead to acute renal failure (ARF). The main principles of tumor lysis syndrome are the identification of high-risk patients, initiation of preventive therapy, and early recognition and intervention of its complications.
Pathophysiology
Tumor lysis syndrome can be precipitated before the initiation of therapy and usually lasts as long as 3 days after the start of chemotherapy, especially with tumors that have a high growth fraction and high sensitivity to chemotherapy. Burkitt lymphoma and T-cell acute lymphoblastic leukemia are most frequently associated with this complication.
Tumor lysis syndrome has also been observed in association with solid tumors, such as hepatoblastoma and stage IV neuroblastoma. From a non-oncologic perspective, intraoperative cardiac arrest secondary to tumor lysis syndrome has been reported after a preoperative splenic artery embolization.1 Although no tumor was present, the patient was noted to have a clinical presentation similar to tumor lysis syndrome, which included hyperkalemia and hyperphosphatemia with ARF and cardiac arrhythmia. No source for the hyperkalemia was identified other than tissue lysis.
In 1980, Cohen et al identified risk factors that predispose patients to metabolic derangements, such as bulky abdominal disease, elevated pretreatment uric acid level, elevated lactate dehydrogenase level, and poor urine output.2 Lysis of tumor cells results in rapid release of potassium, purine nucleic acids, and phosphorus, which leads to hyperkalemia, hyperuricemia, and hyperphosphatemia with secondary hypocalcemia. These metabolic abnormalities can subsequently lead to ARF. These complications may result in multiple organ failure and death.
The kidney is the primary organ involved in the clearance of uric acid, phosphorus, and potassium. Uric acid (pKa = 5.4) is soluble at physiologic pH, but can precipitate in the acidic environment of renal tubules. Hemoconcentration and decreased tubular flow rate within the renal system also contributes to the precipitation of uric acid. Precipitation of uric acid crystals within the collecting ducts and ureters can cause an obstructive uropathy.
The phosphorus content of the lymphoblasts is 3-4 times the content of normal lymphocytes. When these cells lyse as a result of therapy or spontaneous apoptosis, the serum phosphorous rises. The elevated phosphorous can spurn nephrocalcinosis from calcium phosphate crystal precipitation. This occurs in the renal tubules and microvasculature as the in vivo calcium-phosphorus solubility product exceeds 60-70 because of hyperphosphatemia and may be worsened with iatrogenic alkalinization. Symptomatic hypocalcemia may result from hyperphosphatemia.
Frequency
International
Incidence is unknown. Prevalence varies among different malignancies; bulky, aggressive, and treatment-sensitive tumors are associated with higher frequencies of tumor lysis syndrome. In studies of frequency in patients with intermediate-grade or high-grade non-Hodgkin lymphomas, laboratory evidence of tumor lysis syndrome (42%) occurred much more frequently than the symptomatic clinical syndrome (6%).3 In children with acute leukemia receiving induction chemotherapy, silent laboratory evidence of tumor lysis syndrome occurred in 70% of cases, but clinically significant tumor lysis syndrome occurred in only 3%. As advances are made in cancer treatment and more aggressive regimens become in favor, the incidence of tumor lysis syndrome may increase and the syndrome may emerge in a broader spectrum of malignancies.
Mortality/Morbidity
- ARF: Renal tubule precipitation of uric acid, calcium phosphate, or hypoxanthine causes ARF. This often is oliguric (<400 mL/d) in nature, leading to volume overload and complications of hypertension and pulmonary edema. High BUN levels due to increased protein catabolism and renal impairment can be severe enough to result in pericarditis, platelet dysfunction, and defective cellular immunity. Renal dysfunction can be severe enough to require dialysis, but with prompt supportive measures it usually is reversible.
- Cardiac arrhythmia: Hyperkalemia can lead to ECG changes and life-threatening cardiac arrhythmia, including asystole. Severe potassium elevation can cause ECG alterations such as peaked T waves, flattened P waves, prolonged PR interval, widened QRS complexes, deep S wave, and sine waves. Hypocalcemia can lead to QT interval lengthening, which predisposes patients to ventricular arrhythmia.
- Metabolic acidosis: ARF and liberation of large amounts of endogenous intracellular acids from cellular catabolism result in acidemia. This acidemia causes a decrease in serum bicarbonate concentration and a high anion gap acidosis. Acidemic states can worsen the many electrolyte imbalances already present in tumor lysis syndrome; intracellular uptake of potassium is hindered, uric acid solubility is decreased, and extracellular shift of phosphate is promoted. Calcium phosphate solubility, however, improves in acidic conditions. The myriad of metabolic disorders must be assessed and rapidly treated. Proper fluid management, alkalinization of the urine, correction of acidosis, and attention to infections are the mainstays of therapy.
Race
No race predilection is noted.
Sex
No sex predilection is noted.
Age
Although tumor lysis syndrome occurs in all age groups, advanced age is associated with more frequent underlying impaired renal function, which may, in turn, predispose patients to clinically significant tumor lysis syndrome secondary to decreased ability to dispose of tumor lysis byproducts.
Clinical
History
Pertinent historic information in tumor lysis syndrome (TLS) should include the following:
- Time of onset of symptoms of malignancy
- Abdominal pain and distension
- Urinary symptoms, such as dysuria, oliguria, flank pain, and hematuria
- Occurrence of any symptoms of hypocalcemia, such as anorexia, vomiting, cramps, seizures, spasms, altered mental status, and tetany
- Symptoms of hyperkalemia, such as weakness and paralysis
Physical
Symptoms reflect the severity of underlying metabolic abnormalities.
- Hyperkalemia can cause paresthesia, weakness, and fatal cardiac arrhythmias.
- Uremia can manifest as fatigue, weakness, malaise, nausea, vomiting, anorexia, metallic taste, hiccups, neuromuscular irritability, difficulty concentrating, pruritus, restless legs, and ecchymoses. As uremia progresses, paresthesia and evidence of pericarditis may develop, as well as signs of drug toxicity for administered medications eliminated by the kidney. Features of volume overload, such as dyspnea, pulmonary rales, edema, and hypertension, may develop.
- Elevated uric acid levels may present with lethargy, nausea, and vomiting. Rapidly increasing uric acid levels may lead to arthralgia and renal colic.
- Patients with hypocalcemia may present with carpopedal spasms, tetany with positive Chvostek and Trousseau signs, seizures, anxiety, bronchospasm, and cardiac arrest in extreme cases. Deposition of calcium phosphate in various tissues may be responsible for pruritus, gangrenous changes of the skin, iritis, and arthritis.
Causes
- Tumor lysis syndrome occurs most often in patients with acute leukemia with high WBC counts and in those with high-grade lymphomas in response to aggressive treatment. Tumor lysis syndrome may also occur in other hematologic malignancies and in various solid tumors. It has been reported to occur spontaneously, prior to any form of therapy.
- Those at highest risk have bulky, rapidly proliferating tumors that are sensitive to treatment. An elevated pretreatment lactate dehydrogenase (LDH) level, which correlates with high tumor volume, is a strong indicator for developing clinically significant complications of therapy. Presence of renal insufficiency prior to therapy is also correlated with an increased likelihood of tumor lysis syndrome.
More on Tumor Lysis Syndrome |
 Overview: Tumor Lysis Syndrome |
| Differential Diagnoses & Workup: Tumor Lysis Syndrome |
| Treatment & Medication: Tumor Lysis Syndrome |
| Follow-up: Tumor Lysis Syndrome |
| References |
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References
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Further Reading
Keywords
tumor lysis syndrome, TLS, acute tumor lysis syndrome, ATLS, hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, acute renal failure, ARF, Burkitt lymphoma, T-cell acute lymphoblastic leukemia, hepatoblastoma, neuroblastoma, obstructive uropathy, pericarditis, uremia, renal colic, arthralgia, arthritis, hypertension
