Tumor lysis syndrome

In medicine(oncologyand hematology), tumor lysis syndrome is a complication of chemotherapyto particularly large tumors (e.g. bulky lymphomas) and radiation therapy, although it occasionally occurs spontaneously. Breakdown products (lysis) of the cancer cells enter the bloodstream; many are biochemically active substances.

Signs and symptoms

Vomiting, weakness/malaise, decreased urine production, convulsions. Symptoms progress, leading to coma and death if untreated.

In patients who are being treated for massive lesions, prophylaxis with allopurinolmay already have been given (see below).

Diagnosis

Blood testsdone when tumor lysis syndrome is suspected generally include full blood count, renal function(creatinine), electrolytes, blood urea nitrogen, uric acid, calcium, phosphate, and albumin(to correct calcium levels).

Tumor lysis syndrome features elevated uric acid, potassium and phosphate and low calcium due to precipitation with the phosphate.

Pathogenesis

When compared to blood and extracellular fluid, cellsare relatively high in potassium and phosphates, as both are required for cellular function. High turnover of cells leads to an increase in these in the blood.

Uric acid is a breakdown product of DNA, converted by xanthine oxidasefrom xanthine and hypoxanthine, which are in turn purinebreakdown products. Uric acid is more toxic to tissues than (hypo)xanthine. Oddly, goutis not a feature of tumor lysis; the high uric acid levels that cause gout probably need to be present for an extended period of time before the putative crystals can develop.

Prophylaxis and treatment

Follow-up of patients at risk consists of regular checking of urine production and blood pressure, as well as determination of potassium, calciumand phosphatelevels.

Patients with bulky lesions may require intravenous fluids (3 litersa day) and possibly allopurinol, an inhibitor of xanthine oxidase, which limits formation of uric acid. Elimination of waste products may possibly be accelerated by forced alkaline diuresis, e.g. administering bicarbonateto speed up urine production, and diuretics(but thiazidesinterfere with uric acid elimination and must be avoided).

In severe tumor lysis syndrome, individual abnormalities may need immediate treatment.

• Hyperkalemiaand high phosphatelevels may eventually require dialysis
• Hypocalcemiamay require intravenouscalcium gluconateand vitamin D3
• High uric acidmay respond to rasburicase, a synthetic urate oxidaseenzyme. Its role in prophylaxis is undetermined, although the phase II study by Coiffier et al (2003) was favorable.

Reference

• Davidson MB, Thakkar S, Hix JK, Bhandarkar ND, Wong A, Schreiber MJ. Pathophysiology, clinical consequences, and treatment of tumor lysis syndrome. Am J Med 2004;116:546-54. PMID 15063817.
• Coiffier B, Mounier N, Bologna S, Ferme C, Tilly H, Sonet A, Christian B, Casasnovas O, Jourdan E, Belhadj K, Herbrecht R. Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study. J Clin Oncol 2003;21:4402-6. PMID 14581437.

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It uses material from the http://en.wikipedia.org/wiki/Tumor+lysis+syndrome Wikipedia article Tumor lysis syndrome.