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Tumor lysis syndrome (TLS) is a constellation of laboratory and clinical manifestations that can occur spontaneously (before chemotherapy initiation) or after the start of therapy due to lysis of cancer cells and release of intracellular contents in patients with hematologic malignancies. The resulting electrolyte and metabolic disturbances of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia are characteristic of TLS. Risk assessment and prophylactic therapy are critical in preventing this oncologic emergency. In this section we cover the definition, pathophysiology, risk assessment, prevention, and treatment of TLS.

TLS can be defined by clinical or laboratory criteria as described in the table below.

(Source: The Tumor Lysis Syndrome. N Engl J Med 2011.)

In TLS, tumor cell lysis releases large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. The metabolic consequences include hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute kidney injury. The following chart describes the pathophysiology of TLS and associated electrolyte abnormalities.

TLS prophylaxis includes the following strategies:

• laboratory monitoring: Frequency is based on individual risk.

• aggressive hydration: 2500–3000 mL/m²

• maintenance of good urine output (target at least 2 mL/kg/hour): There should be no added potassium in fluids (see hyperkalemia management below). Loop diuretics may be used if urine output is low despite good hydration (contraindicated in hypovolemia or obstructive uropathy). Although sodium bicarbonate was traditionally added to intravenous (IV) fluids to alkalinize the urine, this approach is no longer used.

• reduce uric acid level: Two medications — allopurinol and rasburicase — are often used to reduce uric acid levels.

  • Allopurinol is a xanthine oxidase inhibitor that prevents further formation of uric acid and is often routinely started at diagnosis.

  • Rasburicase is a recombinant urate oxidase that metabolizes existing uric acid and may be administered in patients with markedly high uric acid levels.

Treatment of TLS involves management of the metabolic disturbances as follows:

Management of hyperkalemia:

• Avoid oral and IV sources of potassium.

• Provide continuous cardiac monitoring (with electrocardiogram [ECG], if indicated).

• Administer sodium polystyrene phosphate/sulfonate to help correct elevated serum potassium.

• Administer diuretics to increase potassium excretion (e.g., furosemide, if not contraindicated).

• For severe and/or symptomatic hyperkalemia: all of the above, plus:

  • Administer insulin/dextrose and/or sodium bicarbonate infusion to shift potassium intracellularly.

  • Administer calcium gluconate for cardiac membrane stabilization.

  • Perform dialysis.

Management of hyperphosphatemia:

• Avoid oral sources of phosphorus (low-phosphate diet).

• Administer a phosphate binder.

• Perform dialysis.

Management of hypocalcemia:

• Calcium gluconate infusion should only be used for symptomatic hypocalcemia; routine infusion in patients with asymptomatic low values could precipitate calcium phosphate crystals in the kidneys (especially if the calcium phosphate product is >60 mg²/dL²) and lead to worsening kidney function.

Hyperleukocytosis is defined as an elevated leukocyte count at the time of diagnosis, generally ≥100,000/µL in patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) and ≥200,000/µL in patients with acute lymphoblastic leukemia (ALL). The high number of leukocytes increases risk for TLS and coagulopathy along with neurologic (including stroke) and pulmonary complications secondary to intravascular leukemic thrombi.

Management of hyperleukocytosis includes:

• aggressive hydration and management of tumor lysis

• limited use of blood transfusions to prevent increasing viscosity

• immediate cytoreduction

  • The most effective approach to cytoreduction (leukoreduction) is initiation of chemotherapy. Although low-dose chemotherapy (e.g., hydroxyurea) and leukapheresis (a type of apheresis that separates out the leukocytes) have not been shown to reduce early mortality and are generally not recommended, leukapheresis may be warranted in some clinical situations (e.g., symptomatic leukostasis and when chemotherapy is temporarily contraindicated). Glucocorticoids with or without low-dose chemotherapy can be initiated early for cytoreduction even if the chemotherapy regimen is not definitive.