Tumor Lysis Syndrome

Pathophysiology: Extensive tumor lysis leads to the rapid release of intracellular contents of dying cells with resultant hyperkalemia, hyperphosphatemia and hypocalcemia. Catabolism of nucleic acids leads to hyperuricemia and AKI secondary to uric acid precipitation in tubules, calcium-phosphate precipitation and xanthinuria.

Tumor Lysis Syndrome
Tumor Lysis Syndrome

Diagnosis: Cairo-Bishop classification

Laboratory TLSClinical TLS
Uric acid ≥ 8.0 mg/dLAKI (Cr > 1.5 x upper limit of normal for patient age and sex)
Potassium ≥ 6.0 mEq/dL Cardiac arrhythmia
Phosphorus ≥ 4.6 mg/dLSeizure, tetany, or other symptomatic hypocalcemia
Calcium ≤ 7.0 mg/dL
More than 2 out of 4 lab criteria in the same 24-hour period within 3 days before and 7 days after chemotherapy initiation

Risk Factors for TLS:

Tumor RelatedClinical
High tumor cell proliferation ratePretreatment hyperuricemia (serum uric acid >7.5 mg/dL) or hyperphosphatemia
Chemosensitivity of the malignancyAKI or CKD
High tumor burdenOliguria and/or acidic urine
Elevated pretreatment serum lactate dehydrogenase greater than twice the upper limit of normalDehydration, volume depletion, or inadequate hydration during treatment
Increased ageConcomitant use of drugs that increase uric acid
Bone marrow involvement  
RISK OF TLS IN MALIGNANCY
MalignancyRisk
Solid tumors*Low
Multiple myelomaLow
Chronic lymphocytic leukemia ŧLow
Chronic myeloid leukemiaLow
Burkitt lymphomaHigh
Acute lymphoblastic lymphoma
WBC<100,000/mm3(LDH<2X ULN)
WBC<100,000/mm3(LDH>=2X ULN)
WBC>100,000/mm3

Intermediate
High
High
Acute myeloid leukemia
WBC <25,000/mm3 (LDH<2X ULN)
WBC <25,000/mm3 (LDH>=2X ULN)
WBC 25,000-75,000/mm3
WBC >75,000/mm3

Low
Intermediate
Intermediate
High

*Some solid tumors such as bulky small cell carcinoma are Intermediate/High risk for spontaneous TLS or TLS post treatment

ŧCLL with WBC > 50,000 at initiation of treatment with ibrutinib is associated with intermediate/high risk for TLS

Prophylaxis:

  • Volume Expansion – Target fluid intake of 2-3 L/day with IV or oral therapy before start of chemotherapy to maintain glomerular filtration.  Urine output goal is >2 mL/kg/hr.  Loop diuretics can be used if patients develop volume overload.
  • Avoid urine alkalization- this worsens calcium and phosphate deposition even though it increases uric acid excretion.
  • Hypouricemic agents
    • Allopurinol – Inhibits purine metabolism and increases xanthine and hypoxanthine. It decreases uric acid  production but has no effect on existing uric acid levels. The increase in hypoxanthine and xanthine may lead to xanthinuria, deposition of xanthine crystals in the renal tubules, and AKI.
    • Rasburicase – Recombinant Aspergillus urate oxidase that converts uric acid to allantoin. It is contraindicated in G6PD deficiency.

TLS Prophylaxis Recommendations

TLS RISKMonitoringVolume ExpansionAllopurinolRasburicase
LowX (daily)XX
MediumX (labs q8-12 hrs)XX+/-
HighX (labs q6-8 hrs and cardiac monitoring)XXX

Treatment of confirmed TLS:

  • All patients with confirmed tumor lysis syndrome should be admitted to ICU.
  • Supportive care – Continuous cardiac monitoring, Monitor electrolytes, Cr, Uric acid Q4 – 6hrs, dietary K and phos restriction
  • Rasburicase – Indicated if Uric acid > 8
  • Renal replacement therapy indications (requires HD catheter and coordination with Nephrology)
    • Severe oliguria or anuria
    • Persistent rebound hyperkalemia or hyperphosphatemia
    • Hyperphosphatemia-induced symptomatic hypocalcemia
    • A calcium-phosphate product ≥ 70
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