Tumour Lysis Syndrome

Question 1

TLS : definition

Answer 1

• oncologic emergency
• massive tumour cell lysis
• release of K, P04, nucleic acids –> uric acid into systemic circulation
• occurs with cytotoxic chemotherapy
• can also occur with steroids, radiation, cytolytic antibody therapy
• Cancers:
  
  • high grade lymphoma (Burkitt’s)
  • ALL
  • any cancer with high proliferative rate, large tumour burden, sensitivity to cytotoxic chemo

Question 2

Pathogenesis

Answer 2

• massive quantities of intracellular contents in systemic circulation
• K, P04, nucleic acid (metabolized to uric acid)
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia
• Hyperuricemia
• Acute kidney injury

Question 3

Clinical Manifestations

Answer 3

• Nausea
• Lethargy
• Vomiting
• Diarrhea
• Anorexia
• Hematuria
• Heart Failure
• Cardiac dysrthymias
• Seizures
• Muscle cramps
• Tetany
• Syncope
• Sudden Death

Question 4

Diagnosis of Tumour Lysis Syndrome

Answer 4

2 or more within 3 days before or 7 days after Cytotoxic chemotherapy

• Uric acid 25% increase
• Potassium > 6 or 25% incrase
• Phosphorus > 1.45 mmol/l or 25 % increase
• Calcium < 1.75 mmol/L 25% DECREASE

Clinical diagnosis also includes:

• Increased Creatinine
• Cardiac dysrhythmias
• Seizure

Question 5

Risk factors for TLS

Answer 5

• Hematologic malignancies
• high tumour cell proliferation
• large tumour burden
  
  • bulky disease
  • LDH > 2x ULN
  • bone marrow involvement
• Hyperuricemia pre treatment
• Nephropathy
• Dehydration
• RARE for solid tumours

Question 6

Implicated cancer treatments

Answer 6

• Cytotoxic chemotherapies
• Docetaxal
• Tyrosine kinase inhibitors - pazopanib
• monoclonal antibodies - rituximab

Question 7

Prevention of TLS

Answer 7

• IV hydration
• Loop diuretics
• Hypouricemic drugs
  
  • allopurinol
  • rasburicase
• NaHC03 if metabolic acidosis

Question 8

Treatment TLS

Answer 8

• cardiac monitoring, regular labs q4h
• Rasburicase
  
  • breaks down serum uric acid
• Treat electrolyte abnormalities
  
  • Hyperkalemia
  • Hypocalcemia
  • Hyperphosphatemia
• Hydration +/- loop diuretic
• Renal Replacement Therapy
  
  • oliguria/anuria
  • intractable fluid overload
  • persistent hyperK
  • Symptomatic hypocalcemia