Diagnostic Criteria for Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) is diagnosed when at least two or more serum values of uric acid, potassium, phosphate, or calcium are abnormal at presentation or change by 25% within 3 days before or 7 days after initiation of cancer treatment. 1
Laboratory TLS (LTLS) vs Clinical TLS (CTLS)
TLS is classified into two categories:
Laboratory TLS (LTLS)
LTLS is defined by the presence of at least two of the following metabolic abnormalities:
- Hyperuricemia: Uric acid > upper limit of normal (ULN)
- Hyperkalemia: Potassium > ULN
- Hyperphosphatemia: Phosphate > ULN
- Hypocalcemia: Calcium < lower limit of normal
These abnormalities must occur simultaneously or within 3 days before to 7 days after initiation of cancer therapy 1.
Clinical TLS (CTLS)
CTLS requires:
- The presence of LTLS PLUS
- At least one of the following significant clinical complications:
- Renal insufficiency: Creatinine ≥1.5 × ULN
- Cardiac arrhythmias/sudden death
- Seizures
CTLS is graded based on the severity of the clinical manifestation 1:
- Grade 1-5: Based on the severity of creatinine elevation, cardiac arrhythmias, or seizures
Cairo-Bishop Classification System
The Cairo-Bishop classification is the most widely accepted system for diagnosing TLS 1. This system addresses shortcomings of previous classification systems by:
- Accounting for patients with pre-existing abnormal laboratory values
- Extending the timeframe to include 3 days before and 7 days after therapy initiation
CTLS Grading Scale:
| Complication | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|---|---|---|---|---|
| Creatinine | 1.5 × ULN | >1.5-3.0 × ULN | >3.0-6.0 × ULN | >6.0 × ULN | Death |
| Cardiac arrhythmia | Intervention not indicated | Non-urgent medical intervention | Symptomatic and incompletely controlled medically or controlled with device | Life-threatening | Death |
| Seizure | - | One brief, generalized seizure; well-controlled | Seizure with altered consciousness; poorly controlled | Prolonged, repetitive, or difficult to control seizures | Death |
Monitoring Parameters
For patients at high risk of TLS, the following parameters should be monitored 1, 2:
Every 12 hours for the first 3 days, then every 24 hours:
- LDH
- Uric acid
- Electrolytes (sodium, potassium, phosphorus, calcium)
- Renal function (creatinine, BUN)
For patients with established TLS, monitor every 6 hours for the first 24 hours, then daily:
- Vital parameters (heart rate, blood pressure, urine output, respiratory rate)
- Serum uric acid level
- Serum electrolytes (phosphate, calcium, potassium)
- Renal function (serum creatinine, BUN, urine pH and osmolality, urine specific gravity)
- Blood cell count, serum LDH, albumin, serum osmolality, blood gases, acid-base equilibrium
- Electrocardiogram
- Body weight
Risk Factors for TLS
Identifying patients at risk is crucial for early diagnosis:
Disease-Related Factors:
- High tumor burden
- Highly proliferative malignancies (Burkitt's lymphoma, ALL, AML)
- Bulky disease, especially with liver metastases
- High LDH levels
- Pre-existing hyperuricemia
Patient-Related Factors:
- Dehydration
- Hyponatremia
- Pre-existing renal impairment
- Obstructive uropathy
Clinical Manifestations
TLS may present with various clinical symptoms 1:
- Nausea, vomiting, diarrhea
- Anorexia, lethargy
- Edema, fluid overload
- Hematuria
- Congestive heart failure
- Cardiac dysrhythmias
- Seizures
- Muscle cramps, tetany
- Syncope
Common Pitfalls in TLS Diagnosis
Delayed recognition: TLS can occur before the start of chemotherapy in highly proliferative tumors, not just 12-72 hours after treatment initiation.
Overlooking TLS in solid tumors: While less common, TLS can occur in solid tumors, especially those with high sensitivity to chemotherapy or bulky disease.
Failure to monitor high-risk patients: Inadequate monitoring of laboratory values in high-risk patients can lead to missed diagnosis.
Not recognizing pre-existing metabolic abnormalities: The Cairo-Bishop classification accounts for pre-existing abnormalities, which is important for accurate diagnosis.
Focusing only on hyperuricemia: While hyperuricemia is a hallmark of TLS, the diagnosis requires at least two metabolic abnormalities.
By following these diagnostic criteria and monitoring protocols, clinicians can promptly identify TLS and initiate appropriate management to prevent life-threatening complications.