TUMOR LYSIS Sarah Wede, PharmD

SYNDROME (TLS) PGY1 Pharmacy Resident

OBJECTIVES
•Identify patients at risk of tumor lysis syndrome (TLS)

•Review the criteria for classification of laboratory TLS versus clinical TLS

•Determine roles of IV fluids, allopurinol, and rasburicase in TLS

•Compare the FDA approved dosing of rasburicase with the off-label dosing found on Lexicomp

•Determine why blood samples for the measurement of the uric acid levels need to be placed on
ice in patients who receive rasburicase
DEFINITION
•Rapid release of
cellular components
into the bloodstream
after lysis of malignant
cells occurs leading to
major electrolyte and
metabolic disturbances
RISK FACTORS
•Cancer mass  •Features on patient presentation 
• Bulking tumor or extensive mets  • Nephropathy before diagnosis 
• Organ infiltration by cancer cells  • Dehydration or volume depletion 
• Bone marrow involvement   • Acidic urine 
• Renal infiltration or outflow-tract • Hypotension 
obstruction  • Exposure to nephrotoxins
•Cell lysis potential  • Inadequate hydration 
• High rate of proliferation of cancer cells  •Supportive care 
• Cancer-cell sensitivity to anticancer • Exogenous potassium 
therapy 
• Exogenous phosphate 
• Intensity of initial anticancer therapy 
• Delayed uric acid removal 
TLS DIAGNOSIS Laboratory TLS defined
as two or more
laboratory changes
within three days before
or seven days after
cytotoxic therapy

Clinical tumor lysis

syndrome defined as
laboratory tumor lysis
syndrome plus at least
one clinical complication
DANGERS TO TLS
Hyperphosphatemia and Hypocalcemia 
• Hyperphosphatemia can cause secondary hypocalcemia, leading to neuromuscular irritability (tetany),
dysrhythmia, and seizure, and can also precipitate as calcium phosphate crystals in various organs
(e.g., the kidneys, where these crystals can cause acute kidney injury) 

Hyperkalemia 
• Serious and possibly fatal dysrhythmias  

Hyperuricemia 
• Uric acid can induce acute kidney injury by crystallization, renal vasoconstriction, impaired
autoregulation, decreased renal blood flow, oxidation, and inflammation 
Cytokine Release 
• Possible systemic inflammatory response syndrome and often multiorgan failure 
 HOW TO
MANAGE?
MANAGEMENT
Hydration – to protect kidneys 
• 2500-3000 mL/m2/day
• Add diuretic (high dose furosemide) to assist in urine output 
• Goal urine output 2 mL/kg/hr 

Allopurinol 
• Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric
acid 
• 300 mg daily (max 800 mg oral or 600 mg IV)

Rasburicase 
• Recombinant urate-oxidase enzyme, which converts uric acid to allantoin (an inactive and soluble metabolite of uric
acid)
• Manufacturer's labeling IV: 0.2 mg/kg once daily for up to 5 days 
• Very expensive and not necessary to dose so high
• Actual use: 6 mg or 7.5 mg x 1 dose
• Onset: Uric acid levels decrease within 4 hours of initial administration
• Half-life elimination: ~16 to 23 hours
MANAGEMENT
Hyperphosphatemia Hyperkalemia
• If phosphate > 4.5 in adults • Moderate or asymptomatic (K > 6 mmol/L) 
• Sevelamer at 800 mg TID with • Limit potassium and phosphorus intake during risk period 
meals  • Cardiac monitoring 
• Oral sodium polystyrene sulfonate  
Hypocalcemia • 15 g 1 to 4 times daily 
• Severe and/or symptomatic (K > 7 mmol/L) 
• Asymptomatic • All of the above and/or: 
• No therapy  • Calcium gluconate 100-200 mg/kg via slow IV infusion 
• Symptomatic • Insulin regular 0.1 units/kg + D25 2 mL/kg IV 
• Calcium gluconate 50-100 • Sodium bicarbonate 1-2 mEq/kg IV push  
mg/kg IV administered slowly • Dialysis 
with EKG 
TLS MONITORING
BMP daily at a minimum (as frequent as every
4-6 hours)

Uric acid level – ELITEK level (on ice) daily x

3 days

Phosphorous level daily x 3 days

BONUS QUESTION
Why do you think blood samples for the
measurement of the uric acid levels need to be
placed on ice in patients who received rasburicase?

Without ice, the rasburicase would continue to break

down uric acid in the blood sample and cause a
falsely low level, freezing prevents the ex vivo.
BONUS QUESTION
Why do you think blood samples for the
measurement of the uric acid levels need to be
placed on ice in patients who received rasburicase?

Without ice, the rasburicase would continue to break

down uric acid in the blood sample and cause a
falsely low level, freezing prevents the ex vivo.