Rapid tumor decay syndrome

Rapid tumor lysis syndrome (RTLS), or tumor lysis syndrome (TLS), occurs when a large mass of tumor cells rapidly die.

Causes of rapid tumor lysis syndrome

Most often, SBRO is observed at the beginning of cytostatic therapy in patients:

• with acute and chronic lymphoblastic leukemia and lymphomas (Burkitt's lymphoma),
• in other tumors sensitive to chemotherapeutic, biotherapeutic and radiation treatment,
• Sometimes rapid tumor lysis syndrome develops spontaneously, even before the start of antitumor treatment (Burkitt's lymphoma).

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The mechanism of development of tumor lysis syndrome

Severe metabolic disorders arise due to the destruction of the cell membrane of tumor cells and the entry of intracellular electrolytes (potassium, phosphates) and metabolic products (in particular, purine metabolism - uric acid) into the microcirculatory bed at a rate significantly exceeding their plasma clearance.

Symptoms of rapid tumor lysis syndrome

Symptoms of SBRO vary:

• Brief tonic convulsions and drowsiness caused by hyperphosphatemia and secondary hypocalcemia.
• "Subclinical" arrhythmias.
• ARF is associated with hyperuricemia (uric acid or urate nephropathy) and/or hyperphosphatemia (phosphate nephropathy). In both cases, the renal tubules are primarily affected. The risk of developing ARF is increased in patients with previous renal dysfunction (nephrotoxic chemotherapy, CRF of any etiology) and/or metabolic acidosis and dehydration not corrected before the start of chemotherapy.
• Severe respiratory failure.
• Cardiac arrest due to fatal arrhythmia or hyperkalemia.

Treatment of rapid tumor lysis syndrome

Treatment of SBRO consists of vigorous hydration and correction of electrolyte disturbances, for which aluminum hydroxide, diuretics, HF and other treatment methods are used.

• Aluminum hydroxide is used internally to bind phosphates.
• Conservative treatment of hyperkalemia consists of maintaining high diuresis, hydration and correction of non-gas acidosis.
• Correction of hypocalcemia (secondary to hyperphosphatemia) is carried out only when its symptoms appear and with extreme caution. This is due to the high risk of formation of insoluble calcium phosphate and calcification of soft tissues with a calcium-phosphate product of more than 4.25 mmol ² /l ².
• Effective and relatively rapid correction of metabolic disorders is possible with renal replacement therapy (RRT) using standard dialysate and substitute prescriptions. The purpose of RRT is to eliminate phosphates and uric acid. The procedure requires an appropriate filter and duration. Absolute indications for emergency RRT (or RRT) include hyperuricemia (uric acid level above 10 mg/dl), hyperkalemia (serum potassium above 6.5 mmol/l), hyperphosphatemia, and severe renal failure. ARF due to urate nephropathy is reversible in RRT.

How to prevent rapid tumor lysis syndrome?

Prevention of rapid tumor lysis syndrome is well developed and not labor-intensive, its goal is to prevent renal failure (reduction of uric acid production, non-renal phosphate binding) and increase renal excretion of potassium, phosphates and urates. Preventive measures are necessary for patients with a large mass of tumor tissue and predicted rapid cytolysis. Plasma biochemical markers of rapid cytolysis (potassium, phosphates, calcium, uric acid, lactate dehydrogenase) in patients with a high risk of developing RTS should preferably be studied 2-3 times a day for at least 2 days after the start of cytostatic therapy. For the prevention of rapid tumor lysis syndrome, intravenous administration of isotonic solutions and sodium carbonate, intake of diuretics, allopurinol, rasburicase are indicated.

Hydration with isotonic or hypotonic fluids (0.9% sodium chloride solution, Ringer's solution) in a daily volume of 3000 ml/m2 ⁽ 200-250 ml/h) begins several hours before the administration of cytostatics. Usually, in response to the water-salt load, diuresis increases, and after 2-4 hours the rate of diuresis is equal to the rate of infusion.

In case of severe fluid retention, low doses of loop diuretics (furosemide) or acetazolamide (diacarb) are used at a dose of 5 mg/kg per day.

The development of urate nephropathy can be prevented by maintaining an alkaline urine reaction (pH>7) with intravenous sodium bicarbonate (usually at a dose of 100-150 mEq per liter of infusion solutions). However, an alkaline urine reaction promotes the formation of an insoluble salt (calcium phosphate) in the tubules, so after the start of chemotherapy, the administration of sodium bicarbonate should be limited to cases of decompensated non-gas acidosis.

Allopurinol inhibits the enzyme xanthine oxidase and prevents the conversion of xanthine into uric acid. The drug is prescribed before the start of cytostatic therapy (if possible, 1-2 days before), and allopurinol should be continued after chemotherapy until the uric acid level is normalized (500 mg/m2 ^per day 1-2 days before and during the first 3 days of chemotherapy, and 200 mg/m2 ^per day in the following days). In rare cases (with renal failure), the use of allopurinol is complicated by the development of hyperxanthinuria and xanthine nephropathy. Xanthine is three times less soluble than uric acid and precipitates even with an alkaline urine reaction.

A new drug, rasburicase (modified recombinant uricase), is considered promising in the prevention of urate nephropathy in RTS. Intravenous administration of the drug leads to rapid metabolism of uric acid to much more soluble allantoin, the latter is excreted in the urine. It is assumed that rasburicase promotes the dissolution of uric acid crystals and the resolution of already developed renal failure in RTS; the results of the relevant studies have not yet been published.