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Not everyone treated for cancer will develop tumor lysis syndrome. If you’re receiving cancer treatment, ask your healthcare provider about your risk of developing this condition. Tumor lysis syndrome most often affects people receiving chemotherapy for the following kinds of cancer: Acute lymphocytic leukemia.
How to prevent and manage tumor lysis syndrome?
May 12, 2011 · The higher the level, the greater the risk of the tumor lysis syndrome. Cancer-cell sensitivity to anticancer therapy. Cancers that are inherently more sensitive to therapy have a higher rate of cell lysis and a greater risk of the tumor lysis syndrome than the other cancers. Intensity of initial anticancer therapy.
How is tumor lysis syndrome (TLS) managed?
Feb 02, 2017 · Treatment of established tumor lysis syndrome • Admission to intensive care unit with continuous cardiac monitoring and monitoring of laboratory abnormalities every 4–6 hours • Early nephrology consultation to estimate the indications for renal replacement therapy • Correction of electrolyte abnormalities
How does allopurinol work in tumor lysis syndrome?
May 04, 2015 · Patients at high risk for the development of tumor lysis syndrome should be monitored in the intensive care unit. Established tumor lysis syndrome should be treated in the intensive care unit by aggressive hydration, possible use of loop diuretics, possible use of phosphate binders, use of uric acid lowering agents and dialysis in refractory cases.
What are the risk factors for tumor lysis syndrome (TLS)?
Aug 10, 2021 · Tumor lysis syndrome is most commonly associated with the initiation of cytotoxic chemotherapy. However, there are case reports of tumor lysis syndrome precipitated by radiation therapy, including the use of thalidomide, dexamethasone therapy, and the use of newer chemotherapeutic agents like rituximab and bortezomib. Pathophysiology
What is the cause of tumor lysis syndrome?
Which risk factor is associated with the development of tumor lysis syndrome?
Which drug would be most likely to cause Tumour lysis syndrome?
Which of the following is a key strategy in the prevention of tumor lysis syndrome?
What is tumor lysis syndrome treatment?
How do you prevent tumor lysis syndrome?
Does radiation cause tumor lysis syndrome?
When does tumor lysis syndrome happen?
How does allopurinol prevent tumor lysis syndrome?
Why is allopurinol given before chemotherapy?
How does hydration prevent TLS?
What is tumor lysis syndrome?
The tumor lysis syndrome is the most common disease-related emergency encountered by physicians caring for children or adults with hematologic cancers. 1-4Although it develops most often in patients with non-Hodgkin’s lymphoma or acute leukemia, its frequency is increasing among patients who have tumors that used to be only rarely associated with this complication.5-8The tumor lysis syndrome occurs when tumor cells release their contents into the bloodstream, either spontaneously or in response to therapy, leading to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia.1-3These electrolyte and metabolic disturbances can progress to clinical toxic effects, including renal insufficiency, cardiac arrhythmias, seizures, and death due to multiorgan failure.
Why do you need hydration for tumor lysis?
All patients who are at risk for the tumor lysis syndrome should receive intravenous hydration to rapidly improve renal perfusion and glomerular filtration and to minimize acidosis ( which lowers urine pH and promotes the precipitation of uric acid crystals) and oliguria (an ominous sign).
What is released during lysis of tumor cells?
Lysis of Tumor Cells and the Release of DNA, Phosphate, Potassium, and Cytokines
What is the protocol for acute lymphoblastic leukemia?
For example, some protocols for acute lymphoblastic leukemia begin with a week of prednisone monotherapy , and others begin with a combination of a glucocorticoid, vincristine, asparaginase, and daunorubicin. A patient treated on the latter protocol would have a higher risk of the tumor lysis syndrome.
What is the surrogate for tumor proliferation?
Lactate dehydrogenase level is a surrogate for tumor proliferation. The higher the level, the greater the risk of the tumor lysis syndrome.
How long does it take for a tumor to be lysed?
Laboratory tumor lysis syndrome requires that two or more of the following metabolic abnormalities occur within 3 days before or up to 7 days after the initiation of therapy: hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia.
Which panel of the body is Burkitt's lymphoma?
The highly cellular nature of Burkitt’s lymphoma is evident in Panel B (Burkitt’s lymphoma of the appendix, hematoxylin and eosin). Lysis of cancer cells (Panel C) releases DNA, phosphate, potassium, and cytokines.
What is tumor lysis syndrome?
Tumor lysis syndrome (TLS) is one of the most common cancer therapy complication related to cancer therapy, first described by Bedrna and Polcák3in 1929. TLS is a life-threatening condition with high morbidity and mortality, caused by an abrupt release of intracellular metabolites after tumor cell lysis. This leads to series of metabolic manifestations, especially hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcaemia. Besides seizures and cardiac arrhythmias, acute kidney injury (AKI) is the hallmark of TLS, which determines the clinical outcome. The pathophysiologic mechanism of AKI in TLS was first described by Crittenden and Ackerman.4They described a formation of uric acid crystals in the renal collecting system in patients with disseminated gastrointestinal carcinoma and AKI.
How to treat TLS?
In patients with intermediate and high risk for TLS, vigorous hydration and assessment of fluid balance to keep urinary output >100 mL/h 24 hours before starting chemotherapy and through the duration of treatment are the key to management. Special attention should be paid to elderly patients or those with heart failure. In case of low urine output after achieving an optimal state of hydration, loop diuretics are recommended. Thiazide diuretics that increase uric acid levels and interact with allopurinol should be avoided. Asymptomatic hypocalcaemia should not be treated to avoid increasing calcium phosphate precipitation in the kidneys. Symptomatic hypocalcemia should be treated with calcium gluconate.5
What is Rasburicase used for?
Rasburicase is a recombinant, highly purified urate oxidase enzyme approved for the prevention and therapy of hyperuricemia in pediatric and adult patients . In 2001, Pui et al48were able to show a rapid and sharp reduction of uric acid levels in patients with hematologic malignancies. In many clinical trials, a higher and rapid reduction of uric acid level could be reached using rasburicase compared to allopurinol.49,50
What is the pathophysiological cause of TLS?
Pathophysiological TLS results from a rapid release of intracellular content after tumor cell lysis, which cannot be compensated by cellular buffering and excretory capacity of the renal tubule. This subsequently leads to a variety of biochemical changes causing different clinical manifestations of TLS. Potassium is mainly intracellularly stored, and excessive tumor cell lysis may lead to hyperkalemia. Hyperkalemia is usually the first and most serious abnormality in TLS. It can cause cardiac arrhythmia and sudden death; therefore, laboratory tests should be repeated. Hyperphosphatemia leads to formation of calcium phosphate complexes that may be precipitated in tissues such as renal tubules. The resulting secondary hypocalcemia may cause hypotension, tetany, and muscular cramps together with hyperkalemia and cardiac arrhythmia.5,30
Is TLS a low risk disease?
More recently, increasing incidence of TLS has been reported in the era of highly effective novel anticancer agents like ibrutinib18,19and BCL-2 inhibitors20in diseases like chronic lymphocytic leukemia (CLL), historically considered as being at low risk for developing TLS.
Is TLS a life threatening complication?
TLS is a potentially life-threatening complication of anti-neoplastic therapy. Therefore, prevention is a key principle in TLS management during anticancer therapy. Stratifying patients based on the risk of developing TLS is necessary. Cairo et al33published in 2010 a recommendation to stratify cancer patients at risk to develop TLS. Patients are stratified into three risk groups depending on patient-related factors (preexisting renal dysfunction and hyperuricemia) and disease-related factors (tumor type, tumor burden [represented by tumor stage, white blood cell counts (WBC), and LDH levels]).
Is alkalinization of urine recommended for TLS?
Therefore, alkalinization of urine is not recommended in TLS prophylaxis and therapy anymore.36.
What is tumor lysis syndrome?
Tumor lysis syndrome (TLS) is a major oncometabolic entity requiring emergent recognition and management. TLS comprises a clinicolaboratory derangement of cellular metabolism, which can lead to severe renal impairment, cardiac arrhythmias, seizures, and death[2]. Cellular death mediated by treatment targeted at cancer (chemotherapy or another pharmacological antitumor intervention, embolization of tumor or radiation therapy) or spontaneous cellular death in rapidly dividing cancer cells (which is known as spontaneous TLS) leads to an efflux of cellular material rich in potassium, phosphorus, and uric acid into the bloodstream. However, serum calcium levels typically decrease in patients with TLS because of its binding to excess phosphorus. These key metabolic derangements mediate the acute impairment of renal function, cardiac arrhythmogenicity, central nervous system toxicity, and ultimately death.
How to treat TLS?
First, all patients at intermediate and high risk should be actively hydrated with IV fluids. Coiffier et al[17] recommended patients should be hydrated to maintain urine output of at least 2 mL/kg per hour to minimize the risk of acute kidney injury. The choice of the fluid varies and some recommend the use of dextrose in one quarter normal saline as the initial fluid of choice[17]. However, normal saline or lactated Ringer’s solution are alternative choices, especially if the patient has other conditions such as dehydration, hypovolemia, and hyponatremia (it is essential to remember that lactated Ringer contains potassium and normal saline is associated with hyperchloremic metabolic acidosis)[17]. Also, it is prudent to limit the calcium and potassium content of the IV fluids in such patients. Nevertheless, it is essential to note that some patients with cancer have underlying cardiorenal disease, which puts them at high risk of fluid overload and pulmonary edema. Such patients should be followed in closely monitored settings and there should be a low threshold for initiating loop diuretics if signs of fluid overload appear (shortness of breath, crackles on physical examination, desaturation, etc.). Loop diuretics are preferably used in clinical practice because of their potent diuretic properties as well as their hypokalemic effect, which can be of benefit in patients at risk of TLS. However, to the best of our knowledge there are no published scientific studies assessing the role of diuretics in the treatment of TLS.
What pH is good for TLS?
Urine alkalization is another way of managing patients at risk of TLS. The rationale for this approach lies in the fact that an alkaline urine pH promotes uric acid solubility and its removal[29]. Typically, a carbonic anhydrase inhibitor acetazolamide or sodium bicarbonate are used to reach a urine pH of at least 6.5. However, this approach has not been shown to be superior to the administration of normal saline alone[29]. Furthermore, as mentioned above, in the current era of the widespread use of uric acid lowering agents for TLS prevention, the role of calcium phosphate toxicity increases as a mediator of kidney damage in patients with TLS. In contrast to uric acid crystal deposition in acidic pH, the crystals of calcium phosphate more readily precipitate in alkaline pH, making this approach to alkalization potentially dangerous[30]. Also, an alkaline pH promotes calcium binding to albumin, which can be very dangerous in patients with TLS who tend to have lower calcium levels at baseline, leading to neuromuscular and cardiac toxicity. Therefore, the current role of urine alkalization is of limited value and not recommended for routine use in patients at risk of TLS. It is also important to note that the use of phosphate binders in the prevention of TLS was not specifically studied in the literature. The decision to start phosphate binders should be decided on a case by case basis and always discussed with the patient prior to its initiation. The interested reader is referred to a recently published review on phosphate binders[31].
What is TLS in cancer?
Core tip:Tumor lysis syndrome (TLS) is characterized by a massive tumor cell death leading to the development of metabolic derangements and target organ dysfunction. TLS can occur as a result of cancer treatment or spontaneously. Blood cancers constitute the vast majority of TLS cases because of the sensitivity to therapy and rapid division rates. Solid cancers comprise the minority of cases and are usually advanced if complicated by TLS. Prophylaxis is the mainstay of management and should be routinely implemented in high and intermediate risk patients. Management of established TLS includes intravenous hydration, urate lowering therapies, management of hyperkalemia and hemodialysis in refractory cases.
What are the risk groups for cancer?
We agree with the clinical risk stratification proposed by Cairo et al[15] who stratified cancers into three risk groups: a high risk group, an intermediate risk group, and a low risk group. The high risk group of cancers include advanced Burkitt’s lymphoma/leukemia or early stage disease with elevated baseline LDH, acute lymphocytic leukemia (ALL) with white blood cell (WBC) count ≥ 100000 or less if the baseline elevation of LDH is twice the upper limit of normal (ULN), acute myeloid leukemia (AML) with WBC count ≥ 100000, diffuse large B-cell lymphoma with an elevated baseline LDH of twice ULN, and bulky disease. Intermediate risk malignancies include AML with a WBC between 25000 and 100000, ALL with WBC < 100000 and an LDH of less than twice ULN, early stage Burkitt lymphoma/leukemia with an LDH of less than twice ULN, and diffuse large B-cell lymphoma with a baseline increase in LDH of twice ULN but non-bulky disease. Low risk diseases include indolent lymphomas, chronic lymphocytic leukemia, chronic myeloid leukemia in the chronic phase, AML with WBC count < 25000 and an LDH elevated to less than twice ULN, multiple myeloma, and solid cancers. Therefore, during our risk stratification we paid extra attention to patients with Burkitt’s lymphoma/leukemia, ALL, AML, and diffuse large B cell lymphoma. Furthermore, we have recently reported that TLS in patients with solid malignancies may be higher than previously thought, and certain cancers with a sensitivity to therapy may be at higher risk for TLS, such as small cell lung cancer[4].
What are the biochemical symptoms of TLS?
Therefore, the presentation of these biochemical disorders is typically represented by a clinical constellation of symptoms. For example, patients with TLS who have hypocalcemia may present with such symptoms as nausea, vomiting, muscular hyperactivation such as spasms and tetany, seizures, prolong ation of QT interval on the ECG, cardiac dysrhythmias, and alterations of mental status[12]. Hyperphosphatemia may actually be a key mediator of acute kidney impairment as well as cardiac rhythm disturbances. Patients with hyperkalemia, if symptomatic, present with generalized fatigue, ECG abnormalities[8], and serious cardiac arrhythmias including cardiac arrest. Elevations of uric acid can lead to acute renal insult manifested as an increase in serum creatinine and decrease in urine output.
Is TLS a diagnosis of cancer?
Therefore, it is essential to be highly suspicious if any of the above symptoms a rise in patients with cancer, especially those with tumors in a high risk group In rare instances ( at least in developed countries), TLS may present prior to the diagnosis of cancer. Nevertheless, a clinician should differentiate TLS from other causes of acute kidney injury such as sepsis, obstructive renal disease, medication toxicities (including those of chemotherapeutic agents), use of contrast dye for imaging studies, and rhabdomyolysis, as well as other rarer conditions such as vasculitis and primary glomerulopathies in appropriate clinical scenarios[16]. Thus, a thorough clinical history is of paramount importance when dealing with a cancer patient who has presented with an acute decline in kidney function. The minimum amount of testing should include urinalysis and urine microscopy, comprehensive metabolic panel, uric acid, LDH, complete blood count, and renal ultrasound. The Cairo-Bishop criteria for the diagnosis of laboratory and clinical TLS are presented in Tables Tables11and and2,2, respectively.
What is tumor lysis syndrome?
Tumor lysis syndrome (TLS), an oncologic emergency that typically occurs after the treatment of a malignancy with chemotherapy and/or radiotherapy, is the result of extreme tumor cell lysis with the release of intracellular potassium, nucleic acids, and phosphorus into the systemic circulation. Tumor lysis syndrome occurs most often after administration of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukemia, but it can also occur spontaneously in tumor types that have a high proliferative rate and/or a large tumor burden. The metabolic disturbances of TLS include hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute renal failure. The most important treatment for TLS is prevention. The mainstays of TLS prevention include aggressive hydration, control of hyperuricemia with allopurinol and rasburicase treatment, and close monitoring of electrolyte abnormalities. It is crucial for clinicians to prevent, detect, and treat TLS early to prevent life-threatening complications such as acute renal failure, cardiac dysrhythmia, and seizures. The purpose of this article is to explain the pathophysiology of TLS, identify patients at risk for TLS, and detail strategies for prevention and management of this oncologic emergency.
What are the factors that determine the risk of TLS?
The risk for TLS is derived from many individual factors, including age, type and stage of cancer, lactate dehydrogenase level (LDH), white blood cell (WBC) count, baseline renal function, and patient comorbidities (Cairo et al., 2010) . In order to address risk stratification for TLS, an expert panel of oncologists met in Paris in 2008 to develop criteria to identify patients at low, intermediate, and high risk for TLS (Table 1). Low-risk disease (LRD) was defined as a less than 1% risk of developing TLS, intermediate-risk disease (IRD) was defined as a 1% to 5% risk of developing TLS, and high-risk disease (HRD) was defined as a greater than 5% risk of developing TLS.
How often should I monitor for TLS?
Patients with TLS should generally receive continuous cardiac monitoring as well as measurement of electrolytes and uric acid every 4 to 6 hours (Larson & Pui, 2012b). Treatment is aimed at reversing the electrolyte derangements as well as treating the acute kidney injury. All patients with laboratory and clinical TLS should receive hydration via a central venous catheter as well as rasburicase (Tosi et al., 2008). Rasburicase is administered at 0.20 mg/kg/day for up to 5 days (Kennedy, Koontz, & Rao, 2011). It is contraindicated in patients with a history of glucose-6 phosphate dehydrogenase deficiency, as it will cause hemolysis in that patient population; allopurinol should be substituted (Cairo et al., 2010). The recommended daily dose of allopurinol is 300 mg in patients with a glomerular filtration rate > 50 mL/min (Kennedy, Koontz, & Rao, 2011).
What is hyperphosphatemia in TLS?
Hyperphosphatemia is an additional electrolyte disturbance experienced in TLS that has the potential to cause acute kidney injury. Mild hyperphosphatemia (< 1.62 mmol/L) does not require treatment or can be treated with aluminum hydroxide orally or via nasograstric tube (Tosi et al., 2008). Lowering moderately high serum phosphate levels (> 2.1 mmol/L) can be achieved by administering aggressive IV hydration in addition to phosphate binder therapy (Larson & Pui, 2012b). Some patients may require continuous hemodialysis to correct severe hyperphosphatemia (Cairo & Bishop, 2004). At times, secondary hypocalcemia can occur as a result of hyperphosphatemia. Since the risk of calcium phosphate deposition is high, only patients with symptomatic hypocalcemia require treatment with IV calcium gluconate (Cairo & Bishop, 2004).
How often should TLS be monitored?
Patients at high risk for developing TLS should be assessed for laboratory and clinical signs of the condition every 4 to 6 hours after initiation of chemotherapy. Laboratory monitoring includes evaluation of serum uric acid, phosphate, creatinine, calcium, and LDH levels, in addition to closely monitoring fluid intake and urine output (Coiffier, Altman, Pui, Younes, & Cairo, 2008).
What are the symptoms of TLS?
Uric acid is cleared through the kidneys (Cairo & Bishop, 2004). When hyperuricemia (uric acid level ≥ 7.5 mg/dL) occurs, patients may experience nausea, vomiting, diarrhea, and anorexia as well as acute renal failure (McCurdy & Shanholtz, 2012). Renal failure results from hyperuricemia secondary to uric acid crystal precipitation in the renal tubules (McCurdy & Shanholtz, 2012). At times, flank pain can occur if there is uric acid ureteral stone formation (Larson & Pui, 2012a). In patients experiencing hyperuricemia, urinalysis may reveal uric acid crystals (Larson & Pui, 2012a).
What happens if phosphorus is too high in tumor cells?
In severe hyperphosphatemia, patients may experience nausea, vomiting, lethargy, and seizures (Cairo & Bishop, 2004). When the calcium phosphorus product is greater than 60 mg2/dL2, there is a higher risk of calcium phosphate deposition in the renal tubules as well as the heart (Larson & Pui, 2012). This process can lead to renal failure and cardiac arrhythmias (Larson & Pui, 2012a).