What is tumor lysis syndrome in a patient with a high white blood cell (WBC) count and potential polycythemia vera diagnosis?

What is Tumor Lysis Syndrome?

Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic emergency that occurs when tumor cells undergo rapid lysis—either spontaneously or following cancer treatment—releasing massive amounts of intracellular contents (potassium, phosphorus, nucleic acids, and proteins) into the bloodstream, leading to dangerous metabolic derangements. 1

Pathophysiology

The syndrome develops through a cascade of metabolic events:

• Nucleic acid breakdown: Released nucleic acids are catabolized sequentially to hypoxanthine, then xanthine, and finally to uric acid by xanthine oxidase, resulting in hyperuricemia 1
• Uric acid precipitation: Uric acid crystals precipitate in renal tubules, causing acute kidney injury or renal failure 1
• Electrolyte disturbances: Direct release of intracellular contents causes hyperkalemia, hyperphosphatemia, and secondary hypocalcemia 1, 2
• Clinical complications: These metabolic abnormalities can trigger cardiac arrhythmias, seizures, and sudden death if untreated 2, 3

Classification Systems

TLS is categorized into two distinct types:

Laboratory TLS (LTLS)

• Definition: Presence of two or more abnormal serum values (hyperuricemia >8 mg/dL in adults, hyperkalemia, hyperphosphatemia, or hypocalcemia) occurring within three days before or seven days after initiation of anticancer therapy 1, 2

Clinical TLS (CTLS)

• Definition: Laboratory TLS plus one or more clinical complications, including renal insufficiency (creatinine ≥1.5 times upper normal limit or creatinine clearance <60 mL/min), cardiac arrhythmias, or seizures 1, 2
• Mortality significance: Clinical TLS carries an 83% mortality rate in AML compared to 24% in those without TLS 1

High-Risk Malignancies

TLS occurs most frequently in specific cancer types:

• Highest risk: Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (B-ALL) with 26.4% TLS rate 1
• Very high risk: Acute myeloid leukemia (AML) with white blood cell count >100 × 10⁹/L 1
• Moderate risk: Diffuse large B-cell lymphoma (DLBCL), particularly with bulky disease (>5 cm lymph nodes), with overall NHL TLS rate of 6.1% 1, 4
• Lowest risk: Chronic lymphocytic leukemia (CLL) with TLS in only 0.42% of patients 1

Risk Factors

Disease-Related Factors

• High tumor burden: Bulky disease with large tumor masses, especially lymph nodes >5 cm 1, 4
• Rapid proliferation rate: High-grade hematologic malignancies with extensive bone marrow involvement 1
• Elevated LDH: Levels >2 times upper normal limit indicate high cell turnover 1, 4
• High tumor sensitivity: Cancers highly responsive to chemotherapy 1

Host-Related Factors

• Pre-existing renal dysfunction: Significantly worsens prognosis 1, 4
• Baseline hyperuricemia: Uric acid >8 mg/dL in children or >10 mg/dL in adults 1, 4
• Advanced age and dehydration: Impair renal clearance of metabolites 1
• Obstructive uropathy: Prevents adequate urine flow 1

Clinical Manifestations

Common Symptoms

• Nausea, vomiting, diarrhea, anorexia, and lethargy 2
• Edema, fluid overload, and hematuria 2

Severe Manifestations

• Congestive heart failure and life-threatening cardiac dysrhythmias 2
• Seizures, muscle cramps, tetany, and syncope 2
• Possible sudden death from severe hyperkalemia or cardiac complications 2

Special Consideration: Spontaneous TLS

TLS can occur spontaneously without any cancer treatment, though this is rare:

• More likely in tumors with high proliferative rates and large tumor burden (Burkitt's lymphoma, B-ALL) 4
• Patients with high tumor burden should be monitored even before starting treatment 4
• Risk assessment and prophylaxis should begin immediately upon diagnosis in high-risk patients 4

Context for Polycythemia Vera

In the context of a patient with high WBC count and potential polycythemia vera diagnosis, it's important to note that:

• Polycythemia vera itself carries minimal TLS risk as it is a chronic myeloproliferative disorder with slow cell turnover
• However, if the patient has concurrent acute leukemia (such as transformation to AML) with WBC >100 × 10⁹/L, this represents the highest-risk scenario requiring immediate aggressive prophylaxis 1
• The distinction between polycythemia vera and acute leukemia is critical for TLS risk stratification

Prevention Strategy by Risk Level

High-Risk Patients

• Rasburicase 0.20 mg/kg/day IV over 30 minutes plus aggressive hydration in an inpatient setting 1, 5
• Monitoring every 12 hours for first 3 days, then every 24 hours 1

Intermediate-Risk Patients

• Hydration plus either allopurinol or rasburicase 1, 2

Low-Risk Patients

• Hydration and oral allopurinol 100 mg/m² three times daily (maximum 800 mg/day) 1, 4

Critical Pitfall to Avoid

Never delay cancer treatment without addressing TLS risk first—failure to provide adequate prophylaxis in high-risk patients results in dramatically increased mortality (83% vs 24%) 1. Aggressive hydration should begin 48 hours before tumor-specific therapy when possible, with goal urine output ≥100 mL/hour in adults 1.