What is the clinical presentation of tumor lysis syndrome in adult and pediatric patients with a history of cancer, particularly leukemia or lymphoma, undergoing chemotherapy?

Clinical Presentation of Tumor Lysis Syndrome

Tumor lysis syndrome presents with metabolic derangements (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia) that may progress to life-threatening clinical complications including acute kidney injury, cardiac arrhythmias, seizures, and sudden death. 1

Laboratory Tumor Lysis Syndrome (LTLS)

Laboratory TLS is defined by the presence of two or more abnormal serum values occurring within 3 days before or 7 days after initiation of anticancer therapy: 1

• Hyperuricemia: >8 mg/dL in adults (>8 mg/dL in children) 2
• Hyperkalemia: Potassium levels above normal range 1
• Hyperphosphatemia: Phosphate levels above normal range 1
• Hypocalcemia: Calcium levels below normal range (secondary to hyperphosphatemia) 1

Alternatively, LTLS is present if these values change by 25% from baseline within the specified timeframe. 1

Clinical Tumor Lysis Syndrome (CTLS)

Clinical TLS requires the presence of laboratory TLS plus one or more of the following significant clinical complications: 1, 2

Renal Manifestations

• Acute kidney injury: Serum creatinine ≥1.5 times upper normal limit or creatinine clearance <60 mL/min 2
• Oliguria or anuria: Severe reduction in urine output unresponsive to medical management 2
• Acute renal failure: Results from uric acid precipitation in renal tubules and calcium phosphate deposition 1

Cardiac Manifestations

• Cardiac arrhythmias: Range from brief interventions not indicated to life-threatening arrhythmias with congestive heart failure, hypotension, syncope, or shock 2
• Sudden cardiac death: Can occur from severe hyperkalemia 1
• Palpitations and muscle cramps: Early symptoms from hyperkalemia 3

Neurologic Manifestations

• Seizures: Range from brief generalized seizures to status epilepticus 2
• Neurologic complications: Result from severe electrolyte derangements 4

Timing and Onset

TLS typically develops within 12-72 hours after initiation of cytotoxic therapy, though it can occur spontaneously before treatment or up to 7 days after therapy begins. 1

• Spontaneous TLS (without chemotherapy) is rare but occurs in tumors with high proliferative rates and large tumor burden 5, 6
• Most cases develop within the first 3 days of treatment initiation 1

Clinical Severity and Grading

The grade of clinical TLS is defined by the maximal grade of the clinical manifestation, with CTLS associated with significantly higher mortality (83% vs 24% in those without TLS). 1, 2

• Laboratory TLS alone shows no correlation with increased death rate (21% vs 24%) 1
• Clinical TLS represents a medical emergency requiring immediate intervention 2

High-Risk Presentations

Patients most likely to present with TLS have the following characteristics: 1, 2

• Hematologic malignancies: Particularly Burkitt's lymphoma (26.4% TLS rate in B-ALL), acute lymphoblastic leukemia, and acute myeloid leukemia with WBC >100 × 10⁹/L 1, 2
• Bulky disease: Especially lymph nodes >5 cm or massive liver metastases 2, 3
• Elevated LDH: >2 times upper normal limit 2, 3
• Pre-existing renal impairment: Significantly worsens prognosis 2, 3
• Baseline hyperuricemia: >8 mg/dL in children, >10 mg/dL in adults 2, 5

Common Pitfalls in Recognition

Delayed recognition of TLS in solid tumors carries a mortality rate approaching 35%, higher than in hematologic malignancies, due to lower clinical suspicion and less aggressive prophylactic measures. 3

• TLS can be misdiagnosed due to rapid onset of symptoms that overlap with cancer-derived clinical conditions 7
• Electrolyte derangements may occur before initial presentation to a medical provider, before an oncologic diagnosis has been established 8
• Failing to identify high-risk patients before administering chemotherapy or corticosteroids is a critical error 5