Tumour lysis syndrome: new therapeutic strategies and classification

Abstract

Tumour lysis syndrome (TLS) describes the metabolic derangements that occur with tumour breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular ions, nucleic acids, proteins and their metabolites into the extracellular space. These metabolites can overwhelm the body's normal homeostatic mechanisms and cause hyperuricaemia, hyperkalaemia, hyperphosphaetemia, hypocalcaemia and uraemia. TLS can lead to acute renal failure and can be life-threatening. Early recognition of patients at risk and initiation of therapy for TLS is essential. There is a high incidence of TLS in tumours with high proliferative rates and tumour burden such as acute lymphoblastic leukaemia and Burkitt's lymphoma. The mainstays of TLS prophylaxis and treatment include aggressive hydration and diuresis, control of hyperuricaemia with allopurinol prophylaxis and rasburicase treatment, and vigilant monitoring of electrolyte abnormalities. Urine alkalinization remains controversial. Unfortunately, there have been few comprehensive reviews on this important subject. In this review, we describe the incidence, pathophysiological mechanisms of TLS and risk factors for its development. We summarise recent advances in the management of TLS and provide a new classification system and recommendations for prophylaxis and/or treatment based on this classification scheme.

Tumour Lysis Syndrome: Implications for Cancer Therapy

“…This system makes a distinction between patients who do not require therapeutic medication versus those who experience lifethreatening abnormalities. Cairo and Bishop developed a modified version of the Hande-Garrow classification system in an attempt to address the limitations of this classification system (Cairo and Bishop, 2004). According to this classification, LTLS is considered to be present if two or more serum values of uric acid, potassium, phosphate or calcium are above or below normal and if they change by 25% within 3 days before the start of the therapy or 7 days after the commencement of the treatment.…”

“…The relevant classification is presented in Table 1. CTLS requires LTLS to be present along with'one or more clinical complications such as renal insufficiency, cardiac arrhythmias, and seizures as described in Table 2. The grade of CTLS is defined by the maximal grade of clinical manifestation as detailed in Table 3 (Cairo and Bishop, 2004;Del Toro et al, 2005).…”

“…It is defined as serum uric acid ≥8 mg/dL or 25% increase from baseline 3 days before or 7 days after initiation of chemotherapy (Cairo and Bishop, 2004). Usually developing 48 to 72 hours after therapy, it is caused by increased purine metabolism due to enhanced catabolism of nucleic acids, a consequence of increased turnover or cancer chemotherapy that aggravates cell lysis and causes rapid release of purine metabolites (Arrambide and Toto, 1993;Drakos et al, 1994).…”

“…b Attributed levels: patients will be considered to have elevated levels of creatinine if their probably or definitely to CTLS. Oliguria is defined as an average urine output of <0.5 ml/kg/h for 6 h, (Cairo and Bishop, 2004). considered to be the most dangerous consequence of TLS.…”

Tumor Lysis Syndrome : Authors’ Reply

“…Grading the severity of TLS: Several attempts have been made to classify and grade TLS; a popular one is the CairoBishop grading classification [5]. As per this grading, laboratory TLS is defined as either a 25 % change or level above or below normal, for any two or more serum values of uric acid, potassium, phosphate, and calcium within 3 d before or 7 d after the initiation of chemotherapy.…”