What cancers are at high risk for Tumor Lysis Syndrome (TLS)?

High-Risk Cancers for Tumor Lysis Syndrome

Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (B-ALL) represent the absolute highest-risk malignancies for TLS, with B-ALL patients showing a 26.4% rate of TLS development. 1, 2

Hematologic Malignancies at Highest Risk

Very High-Risk Cancers

• Burkitt's lymphoma: 27% rate of metabolic abnormalities consistent with TLS, with documented fatalities directly attributable to hyperkalemia 1
• B-cell acute lymphoblastic leukemia (B-ALL): 26.4% TLS rate, the single highest among all malignancies 1, 2
• Acute lymphoblastic leukemia (ALL): Overall TLS rate of 5.2%, with hyperuricemia in 21.4% of patients 1
• High-grade non-Hodgkin lymphoma (NHL): Laboratory TLS found in 42% of patients, though clinically significant symptoms requiring specific therapy occurred in only 6% 1

High-Risk Cancers

• Acute myeloid leukemia (AML): 17% overall TLS rate (12% laboratory TLS, 5% clinical TLS), with clinical TLS associated with 83% mortality versus 24% without TLS 1
• AML with hyperleukocytosis (WBC >100 × 10⁹/L): Represents the highest-risk scenario among acute leukemias, requiring immediate aggressive prophylaxis with hydration and rasburicase 2
• Diffuse Large B-Cell Lymphoma (DLBCL): TLS rate of approximately 6.1% in NHL overall, particularly with bulky disease 2

Lower-Risk Hematologic Malignancies

• Chronic lymphocytic leukemia (CLL): TLS suspected in only 0.42% of patients treated with fludarabine, with clinical or laboratory features in just 0.33% 1, 2
• Indolent NHL: Less frequently observed compared to aggressive lymphomas 1
• Acute promyelocytic leukemia: Less frequent TLS occurrence 1

Critical Risk Factors That Elevate TLS Risk

Tumor-Related Factors

• High proliferative rate: Tumors with rapid cell turnover are at substantially increased risk 1, 3
• Large tumor burden: Bulky disease with lymph nodes >5 cm significantly increases risk 2, 4
• Elevated LDH levels: LDH >2 times upper normal limit predicts higher TLS risk 2, 4
• Extensive bone marrow involvement: Increases cellular breakdown potential 2
• High tumor sensitivity to chemotherapy: Rapid response to cytotoxic therapy increases lysis rate 1

Patient-Related Factors

• Pre-existing renal dysfunction: Significantly worsens prognosis and impairs metabolic clearance 2, 4
• Elevated baseline uric acid: >8 mg/dL in children, >10 mg/dL in adults 2, 4
• Dehydration: Impairs renal excretion of metabolites 2
• Advanced age: Increases overall risk 2
• Obstructive uropathy: Compromises renal clearance 2

Solid Tumors with TLS Risk

While TLS occurs most frequently in hematologic malignancies, it is increasingly recognized in solid tumors, particularly those with bulky disease, extensive metastases, or organ/bone marrow involvement. 5 Solid tumors with rapid growth rates and high sensitivity to chemotherapy carry elevated risk. 5

Clinical Implications

Clinical TLS carries an 83% mortality rate in AML patients compared to 24% in those without TLS, emphasizing the critical importance of risk stratification and prophylaxis. 1 Two of four deaths in a Burkitt's lymphoma cohort were directly attributable to hyperkalemia, highlighting the lethal potential of this complication. 1, 6

Common Pitfall to Avoid

Delaying chemotherapy without addressing TLS risk first can result in catastrophic outcomes, as spontaneous TLS can occur even before treatment initiation in high-risk malignancies with large tumor burden and elevated LDH. 2, 4 Patients with high tumor burden should be monitored and receive prophylaxis even before starting treatment. 4