Correction from The New England Journal of Medicine — The Tumor Lysis Syndrome. Correspondence from The New England Journal of Medicine — The Tumor Lysis Syndrome. N Engl J Med. May 12;(19) doi: /NEJMra The tumor lysis syndrome. Howard SC(1), Jones DP, Pui CH. Author information.
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First seizures in adults.
Tumor lysis syndrome: A clinical review
Prophylaxis is the mainstay of management and should be routinely implemented in high and intermediate risk patients. Abstract Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Cellular death mediated by treatment targeted at cancer chemotherapy or another pharmacological antitumor intervention, embolization of tumor or radiation therapy or spontaneous cellular death in rapidly dividing cancer cells which is known as spontaneous TLS leads to an efflux of cellular material rich in potassium, phosphorus, and uric acid into the bloodstream.
Blood cancers constitute the vast majority of TLS cases because of the sensitivity to therapy and rapid division rates. One brief, generalized seizure; seizure s well controlled by anticonvulsants or infrequent focal motor seizures not interfering with ADL. Very high levels of uric acid in the glomerular filtrate may precipitate in the renal tubules, leading to micro-obstruction and vasoconstriction, as well as renal ischemia and up-regulation of inflammatory cytokines, and resulting in an abrupt decrease in the glomerular filtration rate.
Certain parameters should be monitored in individuals at high risk for TLS such as uric acid, phosphorus, potassium, and LDH 4 h after the initiation of chemotherapy or radiation therapy. Given a high cellular turnover in cancer for whatever reason, huge amounts of nucleic acids, purines, and eventually uric acid are released and formed.
Acute Kidney Injury in Patients with Cancer
Hyperphosphatemia may actually be a key mediator of acute kidney impairment as well as cardiac rhythm disturbances. Furthermore, cancer patients often suffer from vomiting and diarrhea, which can significantly diminish their volume status. In conclusion, the clinical presentation of TLS is based on the constellation of individual metabolic derangements in a particular patient.
Also, an alkaline pH promotes calcium binding to albumin, which can be very dangerous in patients with TLS who tend to have lower calcium levels at baseline, leading to neuromuscular and cardiac toxicity.
This approach should be reserved for subjects at intermediate risk of TLS and allopurinol should usually be started simultaneously with rasburicase, unless contraindicated. The clinical presentation and symptomatology is directly linked to the biochemical derangements observed in this disorder. Febuxostat does not require dose modification in patients with renal disease and does not seem to have allergy cross-reactivity with allopurinol[ 20 ].
Table 1 Cairo-Bishop definition of laboratory tumor lysis syndrome for adults. Am J Kidney Dis. Despite being a safe agent, rasburicase should not be used in pregnant or lactating patients due to limited data on safety pregnancy category C drug and excretion into breast milk.
It is necessary to note that laboratory TLS is defined as the presence of at least two or more biochemical variables within the 3 d before chemotherapy or 7 d after chemotherapy in the face of adequate hydration and use of uric acid lowering agent. Potassium and phosphorus should be eliminated from the diet and intravenous IV fluids. The dosage of rasburicase is based on the underlying risk of TLS.
Rasburicase in tumor lysis syndrome of the adult: Tumor lysis syndrome in patients with acute myeloid leukemia: Nephrotoxic effects often develop from overproduction of monoclonal immunoglobulins and free light chains, leading to cast nephropathy the most common cause of acute kidney injurylight-chain—related proximal tubular injury, and various glomerulopathies such as light-chain deposition disease and amyloid light-chain AL amyloidosis. This article has been cited by other articles in PMC.
It is necessary to mention that phosphate binders may be used in patients with hyperphosphatemia in the TLS setting.
Therefore, the current role of urine alkalization is of limited value and not recommended for routine use in patients at risk of TLS. Furthermore, it should not be used on patients with glucose 6 phosphate dehydrogenase deficiency due to the high risk of hemolysis and methemoglobinemia[ 2428 ].
Nevertheless, a clinician should differentiate TLS from other causes of acute kidney injury such as sepsis, obstructive renal disease, medication toxicities including those of chemotherapeutic agentsuse of contrast dye for imaging studies, and rhabdomyolysis, as well as other rarer conditions such as vasculitis and primary glomerulopathies in appropriate clinical scenarios[ 16 ].
In summary, it is recommended that both general and cancer-related factors are included in the risk assessment of every patient. The treatment of fully blown TLS is based on the same principles as its prevention.
The tumor lysis syndrome.
The reader is referred to a detailed review on the management of hyperkalemia[ 32 ]. Uric acid can crystalize and obstruct the flow in the renal tubules, leading to acute kidney injury[ 2 – 410 ]. Safety and efficacy of allopurinol in chronic kidney disease. Similarly, in a recent meta-analysis published by Lopez-Olivo et al[ 24 ], rasburicase was found to be effective in reducing uric acid levels, but it is unclear whether it led to better outcomes for clinical TLS.
In the same way, the approach to seizure in the TLS setting should lysiis exclusion of hypoglycemia and corrected if presentother metabolic abnormalities hypo- or hypernatremia, hypomagnesemiabrain vascular abnormalities hemorrhagic and ischemic strokes, subarachnoid hemorrhage, etc.
Solid cancers comprise the minority of cases and are usually advanced if complicated by TLS. Tumor synndrome syndrome can occur as a consequence of tumor targeted therapy or spontaneously. As discussed above, hyperkalemia may present with peaked narrow-based T waves, prolongation of the PR interval, loss of P waves, prolongation of the QRS interval, and the appearance of so called sine waves[ 8 ].
One aspect of the management of elevated phosphorus in patients with TLS includes the restriction in tumod intake, both in diet and IV fluids. Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy.
However, to the best of our knowledge there are no published scientific studies assessing the role of diuretics in the treatment of TLS.
As discussed above, patients with TLS who have hypocalcemia should not be generally treated with calcium supplementation, given the higher risk of calcium phosphate crystallization and organ injury.
Am J Physiol Renal Physiol. However, calcium should be administered in the case of malignant cardiac arrhythmia such as ventricular tachycardia or fibrillationcardiac arrest, and seizure disorder. Within the kidney, cytokine release associated with acute tubular injury, acute uric acid nephropathy, and acute nephrocalcinosis may contribute to the development of acute kidney injury. Subjects at intermediate and high risk of TLS should be monitored in a hospital setting and possibly in an intensive care unit especially individuals at high risk of TLS.