Tumor Lysis Syndrome

Basics

Description

  • Tumor lysis syndrome (TLS) is a constellation of metabolic derangements resulting when rapid cell destruction of tumor overwhelms metabolic regulation, occurring spontaneously or postanticancer treatment
  • Tumors most at risk for causing TLS:
    • Extremely high in proliferation rate
    • High tumor burden
    • Tumor is markedly sensitive to cytotoxic therapy
    • Can be leukemias, lymphomas or solid tumors
  • TLS typically occurs within 12–72 hr after initiation of cytotoxic chemotherapy
  • Leads to release of intracellular contents:
    • Potassium
    • Phosphate
    • Nucleic acids
  • Hyperkalemia can cause muscle weakness and potentially fatal cardiac arrhythmias
  • Phosphorus binds calcium precipitating calcium phosphate crystals in tissues favoring low solubility:
    • In renal tubules and collecting ducts resulting in obstructive nephropathy, inflammation, and acute kidney injury
    • In myocardial and conduction system tissue interfering with electrical impulse propagation and causing ventricular dysrhythmias
    • Rarely in soft tissues, blood vessels, and possibly lungs contributing to systemic complications
  • Secondary hypocalcemia from phosphate binding to calcium can result in neuromuscular and cardiac dysfunction
  • Nucleic acid breakdown releases uric acid, which can cause AKI via tubular crystal precipitation, obstruction, and renal vasoconstriction
  • Elevated creatinine
  • Acidosis signals more severe disease
  • Lab TLS:
    • Requires the presence of metabolic abnormalities without organ dysfunction
    • Occurs in 10–40% of high-risk patients with hematologic malignancies
    • TLS is defined by the Cairo–Bishop criteria:
      • ≥2 of the following lab abnormalities occurring within 3 d before or 7 d after therapy
      • Uric acid ≥8 mg/dL or a 25% increase
      • Potassium ≥6.0 mEq/L or a 25% increase
      • Phosphorus ≥4.5 mg/dL or a 25% increase
      • Calcium ≤7.0 mg/dL or a 25% decrease
  • Clinical TLS:
    • Lab TLS with organ dysfunction
    • Occurs in 3–7% of high risk tumors
    • Creatinine ≥1.5× upper limit of normal
    • Cardiac arrhythmia
    • Seizure
    • Sudden death

Etiology

Tumors At Risk For Tls

  • Non-Hodgkin lymphoma (NHL) ∼30% of TLS cases:
    • Burkitt lymphoma rare disease but highest risk of developing TLS
  • Acute leukemias ∼30–40% of TLS:
    • Acute myeloid leukemia (AML) (∼19%)
    • Acute lymphoblastic leukemia (ALL) (∼13%)
  • Solid tumors ∼15–20% of TLS:
    • Small-cell lung carcinoma
    • Neuroblastoma
    • Breast cancer
    • Hepatocellular carcinoma
  • Metastatic germ cell tumors

Therapies Leading To Tls

  • Traditional cytotoxic chemotherapy:
    • Standard regimens for ALL, AML, NHL
    • Cytarabine, cyclophosphamide, vincristine, methotrexate
  • Targeted therapies and immunotherapies:
    • Venetoclax
    • Anti-CD20 monoclonal antibodies:
      • Rituximab
      • Obinutuzumab
    • CAR-T cell therapy
    • Tyrosine kinase inhibitors
    • Proteasome inhibitors:
      • Bortezomib
      • Carfilzomib
    • Corticosteroids:
      • Triggers TLS in steroid-sensitive tumors, notably lymphoid malignancies

Spontaneous Tls

  • Occurs in tumors with high proliferation and turnover
  • Radiation therapy
  • Biologic agents:
    • Interferon-α, thalidomide, lenalidomide, or immunomodulators
  • Surgery or embolization of large tumors (rare)

Patient-Related Risk Factors

  • Preexisting renal impairment
  • Dehydration
  • Elevated baseline uric acid
  • Elevated baseline lactate dehydrogenase (LDH)

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