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Tumor lysis syndrome (TLS), or tumor lysis syndrome, is a serious complication of anticancer treatment. It is a specific constellation of metabolic disorders resulting from the rapid breakdown of cancer cells. It is an urgent condition that requires intensive treatment. What is TLS exactly? When is his risk greatest and can he be prevented?
Tumor lysis syndrome(TLS - Englishtumor lysis syndrome ), otherwisetumor lysis syndrome usually takes place in the first days after the initiation of chemotherapy. It is the inclusion of cytostatic drugs that is most often associated with its occurrence. However, it should be remembered that the breakdown of the neoplasm can also happen after radiotherapy or in very rare cases - happen spontaneously, even before treatment.
Tumor lysis syndrome mainly concerns neoplasms characterized by rapid proliferation and, consequently, high sensitivity to chemotherapy. Such features are particularly characteristic of tumors of the haematopoietic system. The highest risk is with acute leukemias and aggressive lymphomas (in particular Burkitt's lymphoma or B-lymphoblastic lymphoma). TLS may occur during the treatment of some solid tumors, but these cases are much less frequent.
Tumor Lysis Syndrome: Symptoms
TLS is caused by anti-cancer treatment and usually occurs up to 3 days after its initiation. Necrosis of tumor cells releases the ions and waste products they contain into the bloodstream. The rapid increase in their concentration in the blood, which exceeds the regulating and excretory capacity of the kidneys, leads to serious disorders. The most important of them are:
- hyperkalemia - elevated potassium levels
- hyperuricemia - increased uric acid levels
- hyperphosphatemia - high levels of phosphates, followed by lowering calcium - hypocalcemia
Hyperkalemia is often the first marker of tumor lysis in laboratory tests. It may occur within hours of starting treatment. Potassium is the main intracellular ion - its concentration is 40 times higher than in the extracellular space. The greatest risk associated with the rapid release of large amounts of itthere are heart rhythm problems including sudden cardiac arrest. Other symptoms of hyperkalemia include: muscle weakness and paralysis, sensory disturbances, and disturbed consciousness.
It is worth remembering that apart from the overt clinical manifestation, the tumor lysis syndrome can also appear as a latent form, the diagnosis of which is possible only on the basis of laboratory tests.
Hyperuricemia, in turn, is the main cause of acute renal failure in the course of TLS. Uric acid is the end product of purine metabolism in the liver. Purine bases are components of nucleic acids - DNA and RNA. Their excess, resulting from the breakdown of tumor cells, leads to an increase in the concentration of uric acid in the blood. It is a weak acid with a narrow solubility range, therefore it can precipitate, especially at acidic urine pH. Uric acid crystals can block the kidney tubules and lead to acute kidney damage. Symptoms of the urinary system may then be: oliguria, colic pain or hematuria.
Another cause of acute kidney failure is tubular obstruction due to the build-up of calcium phosphate crystals resulting from hyperphosphatemia. Precipitation of phosphates leads to a subsequent decrease in calcium levels. Hypocalcaemia has been associated with symptoms of tetany (excessive muscle contraction), vomiting, abdominal cramps, and seizures.
How can cancer lysis syndrome be prevented?
The condition for the implementation of appropriate TLS prophylaxis is to estimate the risk of its occurrence and select a group of patients particularly at risk of this complication. The features of the tumor itself, such as its type, tumor weight and high growth dynamics, are of particular importance for the risk assessment. A useful marker is the measurement of the plasma activity of LDH (lactate dehydrogenase - an enzyme that enters the blood serum as a result of cell death).
The clinical condition of the patient is equally important. In order to avoid acute kidney damage, it is necessary to eliminate as much as possible all the factors that impair their function before starting chemotherapy. These include: dehydration, taking neurotoxic drugs, and previously suffering kidney failure.
Patients can therefore be divided into those with high, intermediate and low risk of tumor lysis syndrome. This classification depends, among others, on frequency of monitoring laboratory parameters (especially those assessing kidney function, electrolyte and uric acid levels) and the intensity of preventive measures.
The most essential elements of preventionTLS is an intensive rehydration system that enables the effective excretion of potassium, uric acid, and phosphate through the urine. In high-risk patients, intravenous fluid intake is required as early as 1-2 days before starting treatment. It should provide a volume of urine output (diuresis) of more than 3 liters per day. It may be necessary to administer diuretics to force diuresis (e.g. in patients with renal failure).
Another goal is to lower uric acid levels to prevent possible uric acid nephropathy. The primary drug is allopurinol. It works by blocking the enzyme xanthine oxidase and thus inhibiting the production of uric acid. Its administration should be started at least 1-2 days before the start of chemotherapy and continued for 10-14 days. An alternative is now a drug of a newer generation - rasburicase. It oxidizes uric acid to allantoin, which dissolves very well in water and is easily excreted through the kidneys. It has a faster onset of action, greater efficiency and a better security profile.
An additional type of treatment, sometimes used in the group of high-risk patients, is the reduction of the intensity of the initial chemotherapy. The slower breakdown of neoplastic cells allows for more effective adaptation of renal regulatory mechanisms and the expulsion of metabolites before they accumulate and lead to organ damage.
How do we treat TLS?
The key role of treatment is prevention and restrictive patient monitoring. This procedure is very effective, but sometimes, despite the preventive measures taken, a full team may develop. If possible, anti-cancer therapy should be suspended until the parameters improve. Therapeutic activities are very similar to those used in prophylaxis, but they are intensified. They mainly consist in the compensation of metabolic disorders. If their correction turns out to be ineffective and, despite appropriate treatment, acute kidney failure occurs - renal replacement therapy is necessary, i.e. dialysis.