Tumor Lysis Syndrome Definition
Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic emergency that occurs when tumor cells undergo rapid lysis—either spontaneously or following cytoreductive therapy—releasing massive amounts of intracellular contents (nucleic acids, proteins, phosphorus, and potassium) into the bloodstream, resulting in hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. 1
Classification System
TLS is formally classified into two distinct categories that guide clinical management:
Laboratory TLS (LTLS): Defined by the presence of two or more abnormal serum values (hyperuricemia, hyperkalemia, hyperphosphatemia, or hypocalcemia) occurring within three days before or seven days after initiation of anticancer therapy 1, 2
Clinical TLS (CTLS): Requires laboratory TLS plus one or more clinical complications including renal insufficiency (creatinine ≥1.5 times upper normal limit), cardiac arrhythmias, or seizures 1, 2
Pathophysiology
The underlying mechanism involves a cascade of metabolic derangements:
Rapid tumor cell death releases nucleic acids that are catabolized to hypoxanthine, then xanthine, and finally to uric acid by xanthine oxidase, resulting in uric acid precipitation in renal tubules and potential acute kidney injury 1
Intracellular potassium, phosphorus, and nucleic acids flood the circulation faster than the kidneys can excrete them, while calcium precipitates with phosphate, causing hypocalcemia 1, 3
These metabolic abnormalities can progress to seizures, cardiac arrhythmias, acute renal failure, neuromuscular abnormalities, hypotension, and death if left untreated 4, 3
Clinical Manifestations
Common symptoms include nausea, vomiting, diarrhea, anorexia, lethargy, edema, fluid overload, and hematuria 2
Life-threatening complications may manifest as congestive heart failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, and sudden death 2, 3
High-Risk Features
Certain disease and patient characteristics dramatically increase TLS risk:
Malignancy-related factors: High-grade hematologic malignancies with rapid proliferation (Burkitt's lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia with WBC >100 × 10⁹/L), bulky disease, extensive bone marrow involvement, and high tumor sensitivity to chemotherapy 1, 2
Laboratory markers: Elevated LDH (>2 times upper normal limit), elevated baseline uric acid, and high white blood cell counts 4, 1
Patient factors: Pre-existing renal dysfunction, dehydration, obstructive uropathy, advanced age, and evidence of TLS before therapy initiation 4, 1
Critical Diagnostic Criteria
Specific laboratory thresholds define TLS components:
- Hyperuricemia: >8 mg/dL in adults and children 1
- Hyperkalemia: Elevated potassium requiring intervention 1
- Hyperphosphatemia: Elevated phosphate levels 1
- Hypocalcemia: Decreased calcium secondary to calcium-phosphate precipitation 1
- Renal failure: Creatinine ≥1.5 times upper normal limit or creatinine clearance <60 mL/min 1
Timing and Incidence
TLS most commonly occurs within 12-72 hours after initiation of cytoreductive therapy, though spontaneous TLS can occur with rapidly proliferating tumors 5, 6
- In non-Hodgkin lymphoma, laboratory TLS occurs in 42% of patients, but only 6% develop clinically significant symptoms requiring specific therapy 2
- Burkitt's lymphoma and B-cell acute lymphoblastic leukemia represent the highest-risk malignancies, with TLS rates of 26.4% in B-ALL 1
- Chronic lymphocytic leukemia carries the lowest risk, with TLS suspected in only 0.42% of patients 1