TLS causes development of conditions such as hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia and hyperuricosuria. The signs and symptoms experienced during TLS occur due to these conditions. The following are the signs and symptoms:
Entire Body System
- Hodgkin Lymphoma
We retrospectively evaluated the efficacy of febuxostat 10 mg in prevention of hyperuricemia associated with TLS (HU-TLS) in 12 patients with non-Hodgkin's lymphoma (NHL). Mean UA levels were found to significantly decrease (p = 0.003). [ncbi.nlm.nih.gov]
TLS management varied by region: 11% of patients in Virginia received uric acid lowering therapy vs 26% in South Carolina (p<0.001) and lymphoma subtype: 11% Hodgkin lymphoma, 26% B-cell non-Hodgkin lymphomas, p<0.001). [ashpublications.org]
A 53-year-old man presented with abrupt oliguria. [ncbi.nlm.nih.gov]
Unfortunately, oliguria and refractory hyperkalemia quickly developed, requiring dialysis. The patient’s condition deteriorated shortly after dialysis, presumably from a large cytokine surge, and he ultimately died. [cmaj.ca]
[…] criteria, and do not require the criteria to occur within the same 24 hour period. 1 Clinical tumor lysis syndrome One or more of the following, in a patient meeting criteria for laboratory TLS: Creatinine increase of ≥ 26.5 μmol/L (≥ 0.3 mg/dL)*** Oliguria [bloodref.com]
A blood test is done to assess the biochemical profile of the patient. This would include analysis of serum potassium, sodium, bicarbonate and chloride. A urine analysis would also be required in order analyze the urinary output and pH. This is done in order to understand the renal functioning. Monitoring of the urinary output is necessary to observe for signs of oliguric renal failure.
In addition to urine and blood tests, imaging studies such as radiography, CT scan and ultrasonography would also be required. Radiography of the chest is carried out to analyze the presence of large cell tumors. CT scan of the abdomen would also be required if these signs of renal failure are noticed. CT scan of the abdomen would also flourish information regarding the presence of mass lesions in the abdominal region.
Patients are also required to be constantly monitored through electrocardiogram in order to observe any changes in the cardiac functioning.
- Creatinine Increased
increase of ≥ 26.5 μmol/L (≥ 0.3 mg/dL)*** Oliguria (< 0.5 mL/kg/h for 6 hours) Symptomatic hypocalcemia**** Cardiac dysrhythmia Seizure Sudden death *** or creatinine ≥ 1.5x age-specific upper limit of reference range if no baseline measurement available [bloodref.com]
TLS is diagnosed as any three or more abnormal serum values: 1) ≥2-fold increase in LDH, 2) ≥50% increase in phosphate, uric acid, or creatinine, 3) ≥30% increase in potassium in the absence of supplementation, and 4) ≥20% decrease in calcium in the absence [jsms.sch.ac.kr]
- Uric Acid Increased
Rasburicase Rasburicase is a recombinant urate oxidase that is responsible for the enzymatic conversion of uric acid to allantoin, which is 5–10 times more soluble than uric acid. [slideshare.net]
Johnson has patents on lowering uric acid as a means to lower blood pressure and improve insulin resistance and a patent application related to lowering uric acid in diabetic renal disease. [journals.plos.org]
- Abnormal Renal Function
Tumour lysis syndrome is associated with high levels of uric acid, phosphate and potassium along with low levels of calcium and abnormal renal function. [ncbi.nlm.nih.gov]
- Peaking T Wave
Severely increased levels may lead to ECG changes, such as widened QRS complexes and peaked T waves, and ultimately ventricular dysrhythmias. [learn.pediatrics.ubc.ca]
Severe potassium elevation can cause electrocardiographic alterations such as peaked T waves, flattened P waves, prolonged PR interval, widened QRS complexes, deep S wave, and sine waves. [emedicine.com]
An EKG demonstrated atrial fibrillation with rapid ventricular response, left anterior fascicular block, and peaked T waves (Figure 3). [hindawi.com]
Treatment of TLS is geared towards stabilizing the basal parameters and correcting the metabolic disorders . If possible, the cancer treatment should be withheld for some time until the condition of the patient stabilizes.
Treatment should be channelized to correct conditions of acute renal failure. The primary therapy includes use of rasburicase wash to eliminate the excess accumulation of uric acid crystals. In conditions when the patient does not respond to such a treatment method, then dialysis should be administered. A dialysis catheter is required in cases of acute renal failure or in conditions of severe hyperkalemia.
Surgery may often be the treatment of choice for central venous line placement.
The prognosis of the disease condition is unfavorable if timely action is not initiated. The preliminary management of TLS includes effective preservation of renal function, neuromuscular irritability and dysrhythmias. Timely recognition of the signs and symptoms of TLS can help prevent the onset of life threatening complications. Failure to initiate prompt management techniques can lead to multiple organ failure and finally lead to death.
Unmanaged and untreated TLS can lead to the following complications:
Tumor lysis syndrome occurs as a result of aggressive treatment in patients with high grade leukemia who also have elevated counts of white blood cells. It is also a common accompaniment in patients suffering from stage 4 neuroblastoma, hematologic malignancies and hepatoblastoma .
Potential candidates for such a syndrome include those patients who have developed tumors that multiply rapidly. In such patients when treatments are employed through radiation therapy, hormonal agents, corticosteroids and monoclonal antibodies, tumor lysis syndrome occurs. The following agents have been known to play a role in the causation of TLS:
The exact prevalence of TLS varies with different type of malignancies, type of tumor cells and the mode of treatment employed. It has been estimated that in patients with high grade non-Hodgkin lymphomas, tumor lysis syndrome was present in 42% of the cases. Children suffering from acute leukemia and receiving induction chemotherapy, TLS occurred in about 70% of the cases.
Tumor lysis syndrome is a common condition for patients suffering from acute leukemia. However, the current literature suggests that the incidence of TLS is increasing as this syndrome is now known to be associated with those malignant tumors that had rare association with such a condition.
TLS occurs as a result of spontaneous reaction or due to aggressive treatment regimens such as chemotherapy and radiation therapy. The dying tumor cells release several components such as nucleic acids, calcium, phosphate and potassium into the circulation. Release of these components causes the levels to raise giving rise to development of hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These conditions can in turn cause respiratory distress, cardiac arrhythmias, seizures and kidney failure causing death .
Various guidelines have been established for preventing the onset of TLS. These include:
- Patients suffering from leukemia or lymphomas and have a high cell turnover rate should be given allopurinol either orally or through the intravenous route. Allopurinol is a xanthine oxidase which inhibits the production of uric acid and thus acts as a preventive medicine for cancer patients. Patients also need to be given IV fluids to increase urinary output.
- Rasburicase is often used for patients who are at a high risk for developing TLS. It is basically a urate oxidase enzyme that is known to degrade the uric acid.
Tumor lysis syndrome, abbreviated as TLS, refers to a group of disorders that occur as a secondary complication to cancer treatment . In such a kind of syndrome, the dying cells release large quantities of various components such as potassium, nucleic acids and phosphate in the blood circulation. These components are basically byproducts of the dying cells as a result of cancer treatment.
Tumor lysis syndrome is more accentuated in cancers that are rapidly responsive to chemotherapeutic treatment . Release of large quantities of these substances gives rise to various associated conditions such as hyperphosphatemia, hyperkalemia and hyperuricemia that occur due to breakdown of nucleic acids . These conditions in turn cause acute renal failure and acute uric acid nephropathy which are potentially fatal . Tumor lysis syndrome is commonly associated in acute leukemias and high grade non-Hodgkin lymphoma .
TLS occurs in cancer treated patients. In such a condition, the dying tumor cells shed off certain components such as potassium, phosphate and nucleic acids. As a result, the levels of these compounds rise and pave way for development of hyperkalemia, hyperphosphatemia and hyperuricemia.
Patients with advanced staged cancers often fall prey to such a condition. In this, large tumor cells that multiply at fast rate often shed off the cellular components causing development of secondary complications. Patients who receive aggressive treatment for cancer are also candidates for TLS.
Blood work is done to reveal the levels of serum potassium, chloride, sodium and bicarbonate. CT scan of the abdomen is also done to analyze the presence of mass lesion in the abdomen. Urine analysis is a necessity to evaluate the urinary output as well as to measure its pH level.
Treatment of TLS includes use of rasburicase to eliminate the accumulation of excessive uric acid crystals. This is done to restore back the renal functioning. In severe cases, surgical intervention may be necessary for placement of central venous line or insertion of dialysis catheter.
- Bishop MR, Cairo MS, Coccia PF. Tumor lysis syndrome. In: Abeloff MD, ed. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:50.
- Jagasia MH, Arrowsmith ER. Complications of hematopoietic neoplasms. In: Wintrobe MM, Greer JP, Foerster J, et al. Wintrobe's Clinical Hematology. Vol II. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2003:1919-44.
- Arrambide K, Toto RD. Tumor lysis syndrome. Semin Nephrol. May 1993; 13(3):273-80.
- Kelly KM, Lange B. Oncologic emergencies. Pediatr Clin North Am. Aug 1997; 44(4):809-30.
- Hande KR, Garrow GC. Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma.Am J Med. Feb 1993; 94(2):133-9.
- Kalemkerian GP, Darwish B, Varterasian ML. Tumor lysis syndrome in small cell carcinoma and other solid tumors. Am J Med. Nov 1997; 103(5):363-7.
- Jaskiewicz AD, Herrington JD, Wong L. Tumor lysis syndrome after bortezomib therapy for plasma cell leukemia. Pharmacotherapy.Dec 2005; 25(12):1820-5.
- Lee CC, Wu YH, Chung SH, et al. Acute tumor lysis syndrome after thalidomide therapy in advanced hepatocellular carcinoma. Oncologist. Jan 2006; 11(1):87-8; author reply 89.
- Abu-Alfa AK, Younes A. Tumor lysis syndrome and acute kidney injury: evaluation, prevention, and management. Am J Kidney Dis. May 2010; 55(5 Suppl 3):S1-13; quiz S14-9.
- Jones DP, Mahmoud H, Chesney RW. Tumor lysis syndrome: pathogenesis and management. Pediatr Nephrol. Apr 1995;9(2):206-12