Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell lysis after initiation of cytotoxic therapy in patients with a large tumor burden, high cancer cell proliferation rate, and chemosensitivity. Incidence of TLS is highest in patients with acute lymphoblastic leukemia, acute myeloid leukemia, non-Hodgkin lymphoma, and Burkitt lymphoma. Solid tumors that are most likely to cause TLS are small cell carcinoma of the lung, breast cancer, and neuroblastoma.

Clinical manifestations include nausea, vomiting, diarrhea, anorexia, lethargy, seizures, muscle cramps, tetany, hematuria, acute renal failure, cardiac arrhythmias, heart failure, syncope, and sudden death. Symptoms are due to the release of large amounts of potassium, phosphate, and nucleic acids into the circulation following the rapid breakdown of tumor cells. Catabolism of nucleic acid produces hyperuricemia, increased uric acid excretion and precipitation of uric acid in renal tubules, resulting in acute kidney injury. Hyperphosphatemia exacerbates acute kidney injury due to deposition of calcium phosphate in renal tubules.

The criteria for the development of TLS were developed by Cairo and Bishop in 2004. They outlined both specific laboratory criteria and clinical diagnostic criteria. Laboratory TLS is defined as any two or more of the following metabolic abnormalities occurring within seven days after initiating chemotherapy: 

• Uric acid 8 mg/dL or higher
• Potassium 6 mEq/L or higher
• Phosphorus 6.5 or higher for children or 4.5 mg/dL or higher for adults
• Calcium 7.0 mg/dL or less

Clinical TLS is defined as laboratory TLS plus one or more of the following: serum creatinine increased 1.5 times the upper limit or more, cardiac arrhythmia, seizure, or sudden death. 

The most significant drawback of this definition is the requirement for the initiation of chemotherapy, because tumor lysis syndrome can develop spontaneously. Another limitation is the use of creatinine levels >1.5 times the upper limit for a patient's age and gender. Patients with chronic kidney disease have elevated levels of serum creatine in the absence of acute kidney injury.

References

Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004;127(1):3-11.

Belay Y, Yirdaw K, Enawgaw B. Tumor Lysis Syndrome in Patients with Hematological Malignancies. J Oncol. 2017;2017:9684909.

Strauss PZ, Hamlin SK, Dang J. Tumor Lysis Syndrome: A Unique Solute Disturbance. Nurs Clin North Am. 2017 Jun;52(2):309-320.