A 25-year-old male with HIV/AIDS and a CD4 count of 65 cells/μL presents to the ED with intractable nausea and vomiting for one week. Laboratory evaluation revealed a white blood cell of 67,000 cells/mm3. An extended chemistry panel reveals creatinine 3.5 mg/dL, potassium 3.0 mmol/L, LDH 250 IU/L, and uric acid 5mg/dL. Calcium and phosphorus were both normal. The patient was admitted for further evaluation and management, and was later diagnosed with Burkitt’s lymphoma.
Tumor lysis syndrome (TLS) is an acute cell lysis of tumor cells with the release of cell content into circulation either spontaneously or in response to therapy, leading to hyperurecemia, hyperkalemia, hyperphosphatemia, and hypocalcemia.1-3
TLS is one of the most common oncology emergencies encountered by hospitalists caring for patients with hematologic malignancies. The incidence and severity of TLS depend on the cell burden, cell proliferation rate, potential for cell lysis or chemo sensitivity, baseline clinical characteristics, and preventive measures taken (see Table 1).2,4
TLS is classified as laboratory or clinical. Laboratory TLS is described as the presence of two or more of the following serum abnormalities at the same time, present within three days before or seven days after the start of therapy.5
- Uric acid >8 mg/dL (475.8 micromole/L) or 25% increase;
- Potassium >6 mEq/L (6 mmol/L) or 25% increase;
- Phosphorus >6.5 mg/dL (2.1 mmol/L) for children or >4.5 mg/dl (1.45 mmol/L) for adults or 25% increase; and
- Calcium >7 mg/dL (1.75 mmol/L) or 25% increase.
Clinical TLS is defined as laboratory TLS in association with increased creatinine levels, seizures, cardiac arrhythmias, or death (see Table 2).5
Tumor cell lysis releases DNA, cytokines, phosphate, and potassium. DNA is metabolized into adenosine and guanosine, which are then converted into xanthines. Xanthines are oxidized by xanthine oxidase into uric acid, which is then excreted through the kidneys.
TLS develops when the accumulation of xanthine, uric acid, potassium, and phosphorus exceeds the kidney’s capacity to excrete them. Cytokines cause hypotension, inflammation, and kidney injury, and worsen the kidney’s excretory capacity. Damage to the kidneys also occurs by renal precipitation of uric acid, xanthine, and calcium phosphate.4
Phosphorus concentrations in tumor cells are four times higher than in normal cells. When the calcium phosphorus product exceeds 60 mg2/dL2, there is an increased risk of calcium phosphate precipitation in the kidney tubules, which could lead to kidney failure. Accumulation of calcium phosphate product may also be cardiotoxic and can lead to cardiac arrhythmias. In addition, hyperphosphatemia can cause secondary hypocalcemia, which may lead to parasthesias, tetany, and cardiac arrhythmias.2,4
TLS is most common in tumors with high proliferative rates and high tumor burden, such as acute lymphoblastic leukemia and Burkitt’s lymphoma, but it can occur with other hematologic malignancies, such as T-cell precursor acute lymphocytic leukemia (ALL), B-cell precursor ALL, acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), anaplastic large cell lymphoma, and plasma cell disorders (e.g. multiple myeloma and plasmacytoma).6,7 TLS has also been reported with the treatment of solid organ nonhematologic tumors (see Table 3).
In hematologic tumors, TLS frequently is associated with cytotoxic chemotherapy, and less frequently with glucocorticoid treatment, monoclonal antibodies (eg, rituximab, bortezomab, imatinib), and radiation therapy.25-29
Patient factors, such as baseline kidney disease or lack of prophylactic/preventive measures for TLS, also increase the risk.4 TLS, however, can develop in patients classified as low risk (see Table 1.