The Tumor Lysis Syndrome - Europe PMC Article. Department of Oncology and International Outreach Program, St. Jude Children’s Research Hospital (S. C. H., C.- H. P.), and the Department of Pediatrics, University of Tennessee Health Sciences Center, College of Medicine (S. C. H., D. P. J., C.- H. P.) — both in Memphis. Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome. Bertrand Arnold Altman. Pretreatment Risk Factors for Tumor Lysis Syndrome in Solid Tumor Patients a. Address reprint requests to Dr. Jude Children’s Research Hospital, 2. Danny Thomas Place, Barry- Longinotti Bldg., MS 7. Memphis, TN 3. 81. Email: gro. edujts@drawoh. The publisher's final edited version of this article is available at N Engl J Med. See other articles in PMC that cite the published article. The tumor lysis syndrome is the most common disease- related emergency encountered by physicians caring for children or adults with hematologic cancers. Although it develops most often in patients with non- Hodgkin’s lymphoma or acute leukemia, its frequency is increasing among patients who have tumors that used to be only rarely associated with this complication. The tumor lysis syndrome occurs when tumor cells release their contents into the bloodstream, either spontaneously or in response to therapy, leading to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. These electrolyte and metabolic disturbances can progress to clinical toxic effects, including renal insufficiency, cardiac arrhythmias, seizures, and death due to multiorgan failure. Although optimal methods of risk classification and treatment have been difficult to define, uniform standards for management of the tumor lysis syndrome are beginning to evolve. Indeed, several groups have advocated guidelines for risk stratification and made recommendations for evaluating risk and for prophylactic therapy for the tumor lysis syndrome. This review of the tumor lysis syndrome summarizes current strategies for risk assessment, prophylaxis, and therapy. The following case illustrates the clinical challenges. CASE REPORTAn 8- year- old boy was referred to an otolaryngologist for tonsillectomy after several months of increased snoring, fatigue, sore throat, enlarged tonsils, and gradually increasing painless and nontender cervical lymphadenopathy. Two days before the scheduled procedure, his parents took him to the local emergency department after he had been unable to sleep because of congestion, sore throat, and difficulty breathing. The physician in the emergency department documented nasal congestion, enlarged tonsils that touched in the midline, and significant anterior and posterior cervical adenopathy. Dexamethasone (4 mg) was administered intramuscularly, and loratadine was prescribed. During the next 3. He returned to the emergency department, where he appeared ill and was found to be moderately dehydrated. Evaluation showed a white- cell count of 8. Chest radiography revealed a small mediastinal mass, and an electrocardiogram was normal. The patient was given two boluses of normal saline (2. Tumor Lysis Syndrome Nejm Pdf FileT- cell acute lymphoblastic leukemia was diagnosed. His course was complicated by oliguria, hyperphosphatemia (a peak of 1. He did not require dialysis, and more than 5 years after diagnosis, he remains in remission. DEFINITION OF THE TUMOR LYSIS SYNDROMEIn the current classification system of Cairo and Bishop,1. Table 1). Laboratory tumor lysis syndrome requires that two or more of the following metabolic abnormalities occur within 3 days before or up to 7 days after the initiation of therapy: hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Clinical tumor lysis syndrome is present when laboratory tumor lysis syndrome is accompanied by an increased creatinine level, seizures, cardiac dysrhythmia, or death. A few refinements could improve this classification.
First, it should be stipulated that two or more metabolic abnormalities be present simultaneously, because some patients may present with one abnormality, but later another one may develop that is unrelated to the tumor lysis syndrome (e. Second, in contrast to Cairo and Bishop’s definition, a 2. Third, any symptomatic hypocalcemia should constitute clinical tumor lysis syndrome. Our patient met the criteria for laboratory tumor lysis syndrome when he returned to the emergency department, and he met the criteria for clinical tumor lysis syndrome the next day, when his creatinine level increased from 1. Hyperkalemia can cause serious — and occasionally fatal — dysrhythmias. Hyperphosphatemia can cause secondary hypocalcemia, leading to neuromuscular irritability (tetany), dysrhythmia, and seizure, and can also precipitate as calcium phosphate crystals in various organs (e. Uric acid can induce acute kidney injury not only by intrarenal crystallization but also by crystal- independent mechanisms, such as renal vaso- constriction, impaired autoregulation, decreased renal blood flow, oxidation, and inflammation. The tumor lysis syndrome (2). 19 nejm.org may 12.pdf Books Audiobooks Comics Sheet Music. Hand-picked favorites from our editors. Editors' Picks Audiobooks. Hand-picked favorites from our editors. OBJECTIVE: To review the risk factors and clinical findings associated with tumor lysis syndrome (TLS) in patients with small cell carcinomas and other solid tumors.METHODS. The new engl and journal of medicine 572 n engl j med 365;6 nejm.org august 11, 2011 hydrogenase (G6PD) deficiency. Rasburicase causes oxidative stress by releasing hydrogen peroxide during the conversion of uric acid to. Tumor lysis also releases cytokines that cause a systemic inflammatory response syndrome and often multiorgan failure. Lysis of Tumor Cells and the Release of DNA, Phosphate, Potassium, and Cytokines. The tumor lysis syndrome occurs when more potassium, phosphorus, nucleic acids, and cytokines are released during cell lysis than the body’s homeostatic mechanisms can deal with. DEFINITION OF THE TUMOR LYSIS SYNDROME. In the current classification system of Cairo and Bishop, 10 the tumor lysis syndrome can be classified as laboratory or clinical (Table 1). Laboratory tumor lysis syndrome. Renal excretion is the primary means of clearing urate, xanthine, and phosphate, which can precipitate in any part of the renal collecting system. The ability of kidneys to excrete these solutes makes clinical tumor lysis syndrome unlikely without the previous development of nephropathy and a consequent inability to excrete solutes quickly enough to cope with the metabolic load. Crystal- induced tissue injury occurs in the tumor lysis syndrome when calcium phosphate, uric acid, and xanthine precipitate in renal tubules and cause inflammation and obstruction (Fig. Tumor Lysis Syndrome Nejm Pdf WriterA high level of solutes, low solubility, slow urine flow, and high levels of cocrystallizing substances favor crystal formation and increase the severity of the tumor lysis syndrome. High levels of both uric acid and phosphate render patients with the tumor lysis syndrome at particularly high risk for crystal- associated acute kidney injury, because uric acid precipitates readily in the presence of calcium phosphate, and calcium phosphate precipitates readily in the presence of uric acid. Also, higher urine p. H increases the solubility of uric acid but decreases that of calcium phosphate. In patients treated with allopurinol, the accumulation of xanthine, which is a precursor of uric acid and has low solubility regardless of urine p. H, can lead to xanthine nephropathy or urolithiasis (Fig. Crystals of Uric Acid, Calcium Phosphate, and Calcium Oxalate. Calcium phosphate can precipitate throughout the body (Fig. The risk of ectopic calcification is particularly high among patients who receive intravenous calcium. When calcium phosphate precipitates in the cardiac conducting system, serious, possibly fatal, dysrhythmias can occur. Acute kidney injury developed in our patient as a result of the precipitation of uric acid crystals and calcium phosphate crystals and was exacerbated by dehydration and acidosis that developed because the tumor lysis syndrome had not been suspected and no supportive care was provided. EPIDEMIOLOGYThe incidence and severity of the tumor lysis syndrome depend on the cancer mass, the potential for lysis of tumor cells, the characteristics of the patient, and supportive care (Table 2). The variability of patient cohorts and lack of standard criteria have contributed to a wide range of reported incidences (see Table 1 in the Supplementary Appendix, available with the full text of this article at NEJM. The greater the cancer mass, the greater the quantity of cellular contents released after the administration of effective anticancer therapy. Cancers with a high potential for cell lysis include high- grade lymphomas, acute leukemias, and other rapidly proliferating tumors. However, the potential for cell lysis must be considered along with the effectiveness of therapy, as highlighted by a case of tumor lysis syndrome in an adult who died after treatment with cetuximab for metastatic colon carcinoma, a cancer in which the tumor lysis syndrome had not been previously reported. Indeed, the tumor lysis syndrome increasingly has been reported in patients with cancers that previously had been rarely associated with this complication, such as endometrial cancer, hepatocellular carcinoma, chronic lymphocytic leukemia, and chronic myelogenous leukemia. Characteristics of patients that confer high risk include preexisting chronic renal insufficiency, oliguria, dehydration, hypotension, and acidic urine. Risk Factors for the Tumor Lysis Syndrome. The adequacy of fluid management affects both the development and the severity of the tumor lysis syndrome. Thus, disastrous cases of the tumor lysis syndrome occurred in patients with nonhematologic cancer who received effective anticancer treatment but no intravenous fluids or monitoring because the tumor lysis syndrome was not anticipated. In contrast, in many countries, patients with a bulky Burkitt’s lymphoma who have a high potential for lysis have a low risk of clinical tumor lysis syndrome because they routinely receive aggressive treatment with hydration and rasburicase, a recombinant urate oxidase enzyme that is a highly effective uricolytic agent (Table 1 in the Supplementary Appendix). Children with Burkitt’s lymphoma who received rasburicase were a fifth as likely to undergo dialysis as those who received allopurinol, illustrating the dramatic difference that supportive care can make, even when other risk factors for the tumor lysis syndrome are the same. This was seen in the 8- year- old boy in the vignette. RISK ASSESSMENTAcute kidney injury is associated with high morbidity and mortality,3. Models that predict the risk of the tumor lysis syndrome have been developed for adults with acute myeloid leukemia.
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