Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors
- Richard A Larson, MD
Richard A Larson, MD
- Editor-in-Chief — Hematology
- Section Editor — Leukemia
- Professor of Medicine
- University of Chicago Pritzker School of Medicine
- Ching-Hon Pui, MD
Ching-Hon Pui, MD
- Chair of the Department of Oncology
- Fahad Al-Rashid Chair of Leukemia Research
- St. Jude's Children's Hospital
- American Cancer Society Professor
- Professor of Pediatrics
- University of Tennessee Health Science Center
- Section Editors
- Reed E Drews, MD
Reed E Drews, MD
- Section Editor — Complications of Cancer
- Associate Professor of Medicine
- Harvard Medical School
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- David G Poplack, MD
David G Poplack, MD
- Section Editor — Pediatric Oncology
- Professor of Pediatrics
- Baylor College of Medicine
Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. Catabolism of the nucleic acids to uric acid leads to hyperuricemia, and the marked increase in uric acid excretion can result in the precipitation of uric acid in the renal tubules and can also induce renal vasoconstriction, impaired autoregulation, decreased renal blood flow, and inflammation, resulting in acute kidney injury. Hyperphosphatemia with calcium phosphate deposition in the renal tubules can also cause acute kidney injury.
TLS most often occurs after the initiation of cytotoxic therapy in patients with high-grade lymphomas (particularly the Burkitt subtype) and acute lymphoblastic leukemia. However, TLS can occur spontaneously and with other tumor types that have a high proliferative rate, large tumor burden, or high sensitivity to cytotoxic therapy.
The pathogenesis, definition, classification, risk factors, etiology, and clinical presentation of TLS will be reviewed here. Prevention and treatment of TLS are discussed elsewhere, as are issues related to treatment of the particular malignancies that are associated with TLS. (See "Tumor lysis syndrome: Prevention and treatment" and "Treatment of Burkitt leukemia/lymphoma in adults" and "Treatment and prognosis of adult T cell leukemia-lymphoma" and "Overview of the treatment of acute lymphoblastic leukemia in children and adolescents", section on 'Tumor lysis syndrome' and "Overview of the complications of acute myeloid leukemia", section on 'Tumor lysis syndrome'.)
In the setting of a malignancy with a high proliferative rate, large tumor burden, and/or a high sensitivity to treatment, initiation of cytotoxic chemotherapy, cytolytic antibody therapy, radiation therapy, or sometimes glucocorticoid therapy alone can result in the rapid lysis of tumor cells. With the emergence of new effective and targeted anticancer drugs or new combinations of drugs, tumor lysis syndrome (TLS) has also been observed in patients with cancers that were previously rarely associated with this complication. (See 'Etiology and risk factors' below.)
This releases massive quantities of intracellular contents (potassium, phosphate, and nucleic acids that can be metabolized to uric acid) into the systemic circulation. The metabolic consequences include hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute kidney injury. High levels of both uric acid and phosphate increase the severity of acute kidney injury because uric acid precipitates readily in the presence of calcium phosphate crystals, and calcium phosphate precipitates readily in the presence of uric acid crystals.
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- CLINICAL MANIFESTATIONS
- DEFINITION AND CLASSIFICATION
- Cairo-Bishop definition
- ETIOLOGY AND RISK FACTORS
- Hematologic malignancies
- Solid tumors
- Spontaneous TLS
- RISK STRATIFICATION
- Risk stratification in acute leukemia