Tumor Lysis Syndrome

What is Tumor Lysis Syndrome (Tls)?

TLS is an acute condition caused by the rapid release of intracellular metabolites from necrotic tumor cells, overwhelming the renal excretory capacity. TLS can occur before therapy in cases with a high tumor cell burden. It usually occurs within 12-48 hours of starting chemotherapy.

Metabolic Complications

• Hyperuricemia
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia
• Acute renal failure
• Metabolic acidosis

Conditions Associated with Tumor Lysis Syndrome (TLS)

Most frequently seen in

Burkitt lymphoma, which carries the highest risk of TLS. Typically associated with hyperuricemia and serum LDH >1500 U/L. Lymphoblastic lymphoma. Leukemias with high TLC

Rarely seen in

Hodgkin's lymphoma

Neuroblastoma

Hepatoblastoma

When seen, it often involves bulky disease (>10 cm) or occurs at advanced stages.

Also read: Rhabdomyosarcoma in Children

Risk for Tumor Lysis Syndrome (TLS) in Various Cancers

Diagnostic Criteria for Tumor Lysis Syndrome (TLS)

Laboratory TLS

Defined by the presence of two or more abnormal serum levels, including:

• Uric acid: ≥ 8 mg/dL
• Potassium: ≥ 6 mEq/L
• Phosphate: ≥ 2.1 mmol/L
• Calcium: ≤ 1.75 mmol/L

OR, a change in serum levels by 25% within 3 days before or 7 days after the initiation of therapy.

Clinical TLS:

Presence of laboratory TLS along with one or more of the following:

• Renal insufficiency
• Cardiac arrhythmia
• Seizures
• Sudden death

Also read: Rare Cancers in Children

Monitoring for Tumor Lysis Syndrome (TLS)

High-risk patients: Monitor serum LDH, uric acid, sodium, potassium, BUN, creatinine, calcium, phosphorus, urine pH, and urine specific gravity. These should be checked every 8–12 hours for the first 3 days, then less frequently as appropriate. Patients with evidence of TLS: Conduct investigations every 6 hours until the condition subsides. CBC every 12 hours, with venous blood gas, ECG, and body weight assessments every 24 hours.

Prevention of Tumor Lysis Syndrome (TLS)

Hydration Therapy:

Ensure adequate hydration. Start hydration with 2L/m²/day at least 24 hours before chemotherapy. Aim for a urine output of 3 mL/kg/hour. Diuretics like furosemide may be considered. Furosemide: 0.5 mg/kg, repeated every 12 hours if necessary.

Drugs:

• Allopurinol (Xanthine oxidase inhibitor): Reduces the conversion of xanthine and hypoxanthine to uric acid. However, it is slow-acting and increases hypoxanthine levels, which can cause acute kidney injury.
• Rasburicase (recombinant urate oxidase): Preferred for high-risk groups. Contra-indicated in G6PD Deficiency

Also read: High-Yield NEET SS Pediatric Oncology Questions

Management of Tumor Lysis Syndrome (TLS)

• Aggressive Hydration: Administer total fluids at 2-4 times the normal maintenance.
• Diuresis: Low-dose furosemide or mannitol (0.5 g/kg) if needed.
• Uric Acid Reduction: Drug of choice: Rasburicase (0.15-0.2 mg/kg/day IV) but contraindicated in G6PD deficiency. Alternative: Allopurinol (200 mg/m2/day IV).
• Leukocyte Reduction: Consider leukapheresis or exchange transfusion if hyperleukocytosis is present.
• Transfusions: PRBC is avoided. Consider FFP for coagulopathy and transfusion if platelet count < 20,000/mm3.
• Chemotherapy: Delay chemotherapy until the patient is stable with adequate urine output.
• Brain Imaging: CT scan for acute hemorrhage. MRI if thrombosis is suspected.

Dialysis in Tumor Lysis Syndrome (TLS)

Indications for dialysis: Progressive renal failure with serum K > 6 mEq/L. Progressive renal failure with serum phosphate > 10 mg/dL. Serum phosphate > 6 mg/dL with metastatic calcification. Oliguria or anuria with eGFR < 50% of expected. Volume overload is unresponsive to diuretics or CCF. Severe metabolic acidosis with pH < 7.0. Hemodialysis is preferred

CRRT is used for unstable patients, as it causes less hypotension but is not effective for reducing phosphate. Dialysis may need to be repeated every 12 hours. Peritoneal dialysis should be avoided.

Also read: What's New In Paediatric Oncology

Management of Various Metabolic Abnormalities

Hyperuricemia

Uric acid > 8 mg/dL is the most common complication of TLS, caused by the breakdown of purines. Can cause precipitation of uric acid crystals in the distal tubules, leading to acute kidney injury (AKI).Management: Adequate hydration with or without urine alkalinization (though alkalinization is less commonly done today).

Hyperkalemia

Potassium > 5 mEq/L, caused by cell lysis and renal dysfunction in TLS.

Management: If serum K is < 6 mEq/L and asymptomatic, treat with hydration, diuresis, and Kayexalate. If serum K is > 6 mEq/L or symptomatic:

• Administer IV calcium gluconate under ECG monitoring.
• Use insulin (0.1 U/kg/hr) and dextrose (0.5 g/kg/hr) IV infusion.
• Administer sodium bicarbonate (1-2 mEq/kg IV).
• Dialysis for refractory cases.

Hyperphosphatemia:

Phosphate > 6.5 mg/dL due to cell lysis and renal dysfunction. Lymphoblasts contain 4 times more phosphate than normal cells. Can cause metastatic calcification and symptoms like pruritus and photophobia.

Management: low-phosphate diet and adequate hydration; avoid urine alkalization. Aluminum hydroxide (150 mg/kg/day), in divided doses every 4-6 hours, reduces gut absorption but does not lower serum phosphate levels. If serum calcium is normal, carbonate can be given orally. Sevelamer (phosphate binder) is an option for older children. Dose 400 mg BD.Dialysis for refractory cases.

Also read: Principles Of Therapy In Children

Hypocalcemia:

Ionized calcium < 1.5 mEq/L, often secondary to hyperphosphatemia, which binds to ionized calcium. Can cause metastatic calcification. Can be asymptomatic or Produce Tetany/ECG Changes.

Management: Address hyperphosphatemia to correct hypocalcemia. If symptomatic, give IV calcium gluconate (10%) 0.5-1 ml/kg slowly over 15-20 minutes under ECG monitoring.

Points to remember 

• Uric Acid Nephropathy
• Precipitation of uric acid crystals is promoted by acidic urine.
• Harrison 20th Edition Says: The finding of Uric Acid crystals in the urine is strong evidence for urea nephropathy. The ratio of Urinary Uric Acid to Urinary Creatinine in patients with acute hyperuricemic nephropathy and<1 in patients with renal failure due to other causes.

Download the PrepLadder app now to access high-yield content with 24-hr Free Trial. Explore premium study resources like Video Lectures, digital notes, QBank, and Mock Tests for a seamless exam preparation. Time to begin your NEET SS Pediatrics Oncology Preparation with PrepLadder.