Diagnostic Criteria for Tumor Lysis Syndrome
Tumor Lysis Syndrome is diagnosed when two or more metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, or hypocalcemia) occur within 3 days before or 7 days after starting cancer treatment, defining Laboratory TLS; Clinical TLS requires Laboratory TLS plus at least one clinical complication (renal failure, cardiac arrhythmia, or seizure). 1, 2
Laboratory TLS Diagnostic Thresholds
The Cairo-Bishop classification system provides specific cutoffs for each metabolic parameter 1, 3:
Hyperuricemia
Hyperkalemia
Hyperphosphatemia
- Phosphorus >1.45 mmol/L (4.5 mg/dL) in adults OR
- Phosphorus >2.1 mmol/L (6.5 mg/dL) in children OR
- 25% increase from baseline 2, 3
Hypocalcemia
At least two of these four abnormalities must be present simultaneously to diagnose Laboratory TLS. 1
Clinical TLS Diagnostic Criteria
Clinical TLS requires Laboratory TLS plus one or more of the following complications 1, 3:
Renal Insufficiency
- eGFR ≤60 mL/min 2
- Calculate using MDRD formula or Cockroft-Gault equation 2
- Critical pitfall: Serum creatinine alone is inadequate because it varies with age, hydration status, and muscle mass; always calculate eGFR 1
Cardiac Complications
Neurological Complications
Timing Window for Diagnosis
The diagnostic window extends from 3 days before to 7 days after initiating anticancer therapy. 1, 2 This addresses a major shortcoming of earlier classification systems that only considered changes within 4 days after treatment, missing patients who develop TLS before therapy or later in the course 1.
Clinical Manifestations to Assess
Beyond the diagnostic criteria, patients may present with 1, 3:
- Nausea, vomiting, diarrhea, anorexia
- Lethargy and edema
- Fluid overload and hematuria
- Congestive heart failure
- Syncope
- Symptoms typically appear 12-72 hours after chemotherapy initiation 1
Initial Diagnostic Workup
Baseline Laboratory Assessment
Before treatment in at-risk patients, obtain 1:
- LDH (elevated levels predict TLS risk) 1
- Uric acid, potassium, phosphorus, calcium
- Creatinine and BUN
- Comprehensive metabolic panel 1
- Sodium and albumin
Risk Stratification Factors
Tumor-related high-risk features 2, 3:
- Burkitt's lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia
- High proliferation rates and tumor burden
- Elevated baseline LDH
Patient-related high-risk features 2, 3:
- Pre-existing hyperuricemia (≥8 mg/dL confers 11.66-fold increased risk) 1
- Pre-existing renal dysfunction
- Advanced age
- Tumor infiltration in kidneys
Monitoring Protocol
High-Risk Patients (Before TLS Develops)
Monitor every 12 hours for first 3 days, then every 24 hours 1, 2:
- LDH, uric acid, sodium, potassium
- Creatinine, BUN, phosphorus, calcium
Established TLS Patients
Monitor every 6 hours for first 24 hours, then daily 1, 2:
- Vital signs (heart rate, blood pressure, urine output, respiratory rate)
- Serum uric acid and electrolytes (phosphate, calcium, potassium)
- Renal function (creatinine, BUN, urine pH, osmolality, specific gravity)
- ECG, blood gases, acid-base status every 24 hours 1
Common Diagnostic Pitfalls
Do not rely on serum creatinine alone for renal assessment—always calculate eGFR using validated formulas 1, 2. The original Hande-Garrow classification system had significant limitations by requiring 25% increases from baseline, which failed to capture patients with pre-existing abnormal values 1.
Do not miss spontaneous TLS occurring before treatment initiation, particularly in highly proliferative tumors 4, 5. The Cairo-Bishop criteria specifically include the 3-day pre-treatment window to capture these cases 1.