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Essentials of Diagnosis

  • Due to tumor cell lysis (TLS), commonly in high-risk hematologic malignancies and/or tumors with large cellular burden.

  • Results when intracellular contents of nucleic acids, potassium, phosphorus are rapidly released into the bloodstream.

  • Characterized by laboratory findings of hyperuricemia, hyperkalemia, hyperphosphatemia, and/or hypocalcemia with clinical manifestations of renal, cardiac, and/or neurologic dysfunction.

  • Knowledge of risk factors of TLS and early detection of TLS are imperative to implementing preventive and therapeutic strategies to reduce morbidity and mortality.


Tumor lysis syndrome (TLS) is a common emergency in clinical oncology. TLS describes a constellation of metabolic abnormalities resulting from the release of intracellular contents into the bloodstream, either spontaneously or more commonly during chemotherapy-induced tumor cell lysis. Cell lysis ultimately results in the characteristic findings of TLS which include hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Clinically, these metabolic derangements can present as acute kidney injury (AKI), cardiac arrhythmias, seizure, and lead to significant morbidity and mortality.

The classification of TLS is divided into laboratory and clinical TLS (Table 13–1). These schemas were first defined by Hande and Garrow in 1994 and were modified and expanded 10 years later by Cairo and Bishop. Cairo and Bishop define laboratory TLS as the presence of two or more of the classic metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia) within 3 days before, or up to 7 days following the administration of chemotherapy, despite adequate volume expansion and the use of hypouricemic agents. The specific values which fulfill diagnostic criteria of laboratory TLS are provided in Table 13–1. Clinical TLS is defined by laboratory TLS accompanied by renal, neurologic, or cardiac dysfunction which is not a direct result of chemotherapy itself. Cairo and Bishop also provide a grading system to assess the severity of TLS based on a 0–5 scale, taking into account the severity of the clinical manifestations (Table 13–2). In 2011, Howard et al. offered modifications to the standard Cairo–Bishop definition of TLS, specifying the simultaneous presence of two or more metabolic abnormalities at the time of diagnosis for the definition of laboratory TLS. They also challenge the criterion of 25% increase from baseline as it may not always be clinically relevant if the baseline value is normal. Last, they also propose that symptomatic hypocalcemia should be included in the definition of clinical TLS. Various groups have objected that the Cairo and Bishop criteria exclude spontaneous TLS, potentially limiting the recognition of severe metabolic disturbances that have the potential for severe patient morbidity. Others have debated that the Cairo–Bishop definition of renal dysfunction of creatinine greater than 1.5 times the upper limit of normal should be replaced with an increase of 0.3 mg/dL in creatinine or a relative 50% increase in baseline creatinine, to better reflect standardized definitions of AKI.

Table 13–1.The Cairo–Bishop definition of laboratory and clinical tumor lysis ...

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