Tumor lysis syndrome
(Redirected from Tumor Lysis Syndrome (TLS))
Background
- Typically occurs within 1 to 5 days of initiation of chemotherapy
- Associated with treatment of acute leukemia, Burkitt lymphoma, NHL
- Rarely observed in solid tumors or without prior therapy
- Rapid turnover of tumor cells (spontaneously or after treatment) leading to release of:
- Potassium
- Phosphate
- Binds Ca causing hypocalcemia
- Uric acid (converted from nucleic acids)
Risk Factors
- High cell proliferation rate
- Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
- Extensive BM involvement
- Tumor infiltration of the kidney
Cairo-Bishop Definition[1]
Laboratory Tumor Lysis Syndrome
- Abnormality in 2 or more of the following, occurring within 3d before or 7d after chemo:
- Uric acid ≥ 8mg/dL or 25% increase from baseline
- Potassium ≥ 6mEq/L or 25% increase from baseline
- Phosphate ≥ 4.5mg/dL or 25% increase from baseline (≥ 6.5 for children)
- Calcium ≤ 7mg/dL or 25% decrease from baseline
Clinical Tumor Lysis Syndrome
- Laboratory tumor lysis syndrome plus 1 or more of the following:
- Creatinine > 1.5 times upper limit of age-adjusted reference range
- Cardiac dysrhythmia or sudden death
- Seizure
Clinical Features
- Hyperuricemia
- Hyperkalemia
- Most immediate life-threatening element (due to dysrhythmias)
- Hyperphosphatemia
- May combine with Ca to precipiate in renal tubules
- Hypocalcemia
- Acute Renal Failure
- Most common cause of morbidity
- Usually results from uric acid precipitation within renal tubules
Differential Diagnosis
Oncologic Emergencies
Related to Local Tumor Effects
- Malignant airway obstruction
- Bone metastases and pathologic fractures
- Malignant spinal cord compression
- Malignant Pericardial Effusion and Tamponade
- Superior vena cava syndrome
Related to Biochemical Derangement
- Hypercalcemia of malignancy
- Hyponatremia due to SIADH
- Adrenal insufficiency
- Tumor lysis syndrome
- Carcinoid syndrome
Related to Hematologic Derangement
Related to Therapy
- Chemotherapy-induced nausea and vomiting
- Cytokine release syndrome
- Chemotherapeutic drug extravasation
- Differentiation syndrome (retinoic acid syndrome) in APML
- Stem cell transplant complications
- Catheter-related complications
- Tunnel infection
- Exit site infection
- CVC obstruction (intraluminal or catheter tip thrombosis)
- Catheter-related venous thrombosis
- Fracture of catheter lumen
- Oncologic therapy related adverse events
Evaluation
Work Up
- CBC
- Chemistry
- Elevated Cr
- Calcium, phosphate
- Uric Acid
- LDH - >2-3 fold increase stratifies into higher TLS risk[2]
- Urinalysis
- ECG
- Avoid IV contrast
Management
Aggressive hydration - Goal urine output is 3L in 24hr
Hypocalcemia Treatment
- ≤7 or 25% decrease in baseline
- Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition), such as widened QRS or ventricular arrhythmias
- Calcium gluconate 50-200mg IV
Hyperphosphatemia treatment
- Treat the underlying cause
- Restrict calcium phosphate intake
- IV Normal Saline (if normal renal fx)
- Acetazolamide (500mg IV q6hr) - if normal renal function
- Phosphate Binder - Aluminum hydroxide (50-150mg/kg PO q4-6h) - limited effect
- Dialysis if refractory
- Consider sevelamer 800-1600mg PO tid to avoid side effects of aluminum toxicity and hypercalcemia from aluminum hydroxide treatment
Hyperuricemia Treatment
- ≥8 or 25% increase
- Allopurinol
- Acts slowly; only helpful for preventing future production of uric acid
- 10mg/kg/d PO q8 OR 200-400mg/m2 IV q12; renally dosed
- Inhibition of xanthine oxidase can last 18-30h
- Urate Oxidase
- Rasburicase 0.05-0.2mg/kg IV
- Can be used for BOTH prevention and treatment
- Uric acid final product of purine metabolism
- Urate oxidase converts uric acid to allantoin (5-10x more soluble)
- Allopurinol
Hyperkalemia Treatment
- Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
- Giving Ca leads to increased Ca/phos deposition which leads to renal failure
- See Hyperkalemia for treatment options
Dialysis Criteria
- Potassium >6
- Significant renal insufficiency (Creatinine >10)
- Uric Acid >10
- Symptomatic hypocalcemia
- Serum phosphorus >10
- Volume overload
Disposition
- Admit (often to ICU)