TLS was found in Early recognition and treatment is essential to avoid morbidity and mortality. Tumor lysis syndrome TLS is an oncological emergency resulting from massive lysis of malignant cells and clinically characterized by renal failure, seizures and cardiac arrhythmias that requires early recognition and management. The massive lysis of lymphoblastic cells releases intracellular metabolites like potassium K , uric acid UA , phosphate P and products of protein and purine metabolites into systemic circulation.
These high effluxes of metabolites result in abnormal accumulation in the blood and exceed the capacity of renal clearance and results hyperkalemia, hyperuricemia, hyperphosphatemia and secondary hypocalcemia. Hyperuricemia is the initial and most common abnormality, induces acute renal injury by intra-renal uric acid crystallization and It aggravates precipitation of calcium phosphate crystals in the renal tubules.
This crystal nephropathy causes inflammation, obstruction and renal tubular damage ultimately manifesting as acute kidney injury. Hyperkalemia may also be aggravated by crystal nephropathy induced AKI and may cause serious dysrhythmias and death.
Hypocalcemia may lead to muscle cramps, tetany, seizures and dysrhythmias. There is concomitant rise of lactic dehydrogenase because of rapid cell turn over in ALL. More aggressive nature, rapidly proliferating tumor, with high leukemic burden and highly sensitive to drug treatment and high-risk patients are more likely to develop TLS.
ALL is most aggressive malignancy associated with high mortality Since TLS is an acute emergency so early identification of high-risk patients, appropriate prophylactic interventions like hyper hydration, use of allopurinol, rasburicase and strict monitoring for its clinical complications like arrhythmia, AKI and central nervous system CNS manifestations in leukemic patients undergoing chemotherapy may help to decrease frequency, severity of TLS and improve outcome.
We want to share our retrospective data of last two years, focusing on this serious complication of ALL in children. Laboratory TLS was defined when two or more of the following biochemical abnormalities were present i hyperuricemia ii hyperkalemia iii hyperphosphatemia iv hypocalcemia, Clinical TLS was diagnosed if child had abnormality in any one end organ eg AKI, seizure and cardiac arrhythmias along with lab TLS. Patients were categorized according to The National Cancer Institute NCI criteria into standard risk and high -risk groups, based on age at diagnosis, initial white blood count WBC , central nervous system or testicular involvement.
Patients were classified into precursor -B leukemia pre-B Cell and precursor T-cell leukemia pre-T-Cell , based on flow cytometry and immunohistochemistry. Patients who received initial chemotherapy at other institute and not underwent induction phase or refused chemotherapy were excluded. Data collected included bio-data, anthropometry, various clinical and laboratory parameters from hospital record in the predesigned proforma.
The laboratory parameters included complete blood picture, UA, P, Ca, SCr and K measured as baseline day 0 then daily after initiation of chemotherapy till 7 th day. Ethical approval was taken from hospital ethical committee. For numerical variables like age, S.
Cr, S. Data was entered in SPSS version Independent t- test was used for comparison of means. Data of 91 patients were included in this study. Fifty-two Majority of patients 73, The mean height and weight of patients with ALL were The mean body surface area was 0.
Majority On risk stratification, 56 Create Account. Advanced Search. Skip Nav Destination Article Navigation. Close mobile search navigation Article navigation. Volume 41, Issue 1. Previous Article Next Article. Article Navigation. Articles January 01 Tumor Lysis Syndrome Thomas B. Russell, MD ; Thomas B. Causes: High turnover within tumor cells produces intracellular purine nucleic acids.
With cell lysis, the uric acid that is produced from purine catabolism is released, and accumulates in the renal collecting duct. The resulting nephropathy may be further exacerbated by pre-existing renal insufficiency i. Causes: Low calcium levels may result from calcium phosphate precipitation, and therefore often occurs concurrently with hyperphosphatemia. Guidelines for the new management of pediatric and adult tumor lysis syndrome: an evidence-based review.
J Clin Oncol ; 26 16 Zonfrillo MR. Management of pediatric tumor lysis syndrome in the emergency department. Several weeks after the treatment of hypocalcemia with multiple doses of intravenous calcium carbonate administered by means of a peripheral intravenous catheter in the dorsum of the hand, ectopic calcification was confirmed radiographically arrows.
Calcium phosphate can precipitate throughout the body Fig. The risk of ectopic calcification is particularly high among patients who receive intravenous calcium. 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.
The 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.
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.
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.
Models that predict the risk of the tumor lysis syndrome have been developed for adults with acute myeloid leukemia 35 , 36 and children with acute lymphoblastic leukemia 37 treated with hydration and allopurinol but not rasburicase.
These models lack a standard definition of the tumor lysis syndrome, use different primary end points i. Experts have issued management guidelines for the tumor lysis syndrome, 2 , 9 , 38 but further guidance awaits simple risk-prediction models that have a standardized definition of the tumor lysis syndrome and uniform supportive care guidelines for each cancer type. This algorithm presents a guide to care at the time of patient presentation.
Subsequent care depends on how the patient progresses. The tumor lysis syndrome unexpectedly develops in some patients who are at low risk, and they require more aggressive treatment, and some high-risk patients have no evidence of the tumor lysis syndrome after a few days of treatment and need less intensive care after the initial period.
Assessment of risk factors for the tumor lysis syndrome requires clinical judgment. It may not always be clear whether mild or transient dehydration should count, whether a cancer mass is medium or large, or whether the potential for cell lysis of a particular cancer with a particular treatment is medium or high.
If it is difficult to distinguish between two categories, treat the patient as if he or she is in the higher-risk category. Because the algorithm presented is designed for use by both oncologists and non-oncologists, a conservative approach is presented to maximize safety. TLS denotes tumor lysis syndrome. Optimal management of the tumor lysis syndrome should involve preservation of renal function. Management should also include prevention of dysrhythmias and neuromuscular irritability Fig.
All patients who are at risk for the tumor lysis syndrome should receive intravenous hydration to rapidly improve renal perfusion and glomerular filtration and to minimize acidosis which lowers urine pH and promotes the precipitation of uric acid crystals and oliguria an ominous sign.
This is usually accomplished with hyperhydration by means of intravenous fluids to ml per square meter per day in the patients at highest risk. Hydration is the preferred method of increasing urine output, but diuretics may also be necessary.
In a study involving a rat model of urate nephropathy with elevated serum uric acid levels induced by continuous intravenous infusion of high doses of uric acid, high urine output due to treatment with high-dose furosemide or congenital diabetes insipidus in the group of mice with this genetic modification protected the kidneys equally well, whereas acet-azolamide mild diuresis and bicarbonate provided only moderate renal protection no more than a low dose of furosemide without bicarbonate.
Reducing the level of uric acid, with the use of allopurinol and particularly with the use of rasburicase, can preserve or improve renal function and reduce serum phosphorus levels as a secondary beneficial effect. The level of uric acid may take 2 days or more to decrease, a delay that allows urate nephropathy to develop Fig.
Moreover, despite treatment with allopurinol, xanthine may accumulate, resulting in xanthine nephropathy. By preventing xanthine accumulation and by directly breaking down uric acid, rasburicase is more effective than allopurinol for the prevention and treatment of the tumor lysis syndrome.
In a randomized study of the use of allopurinol versus rasburicase for patients at risk for the tumor lysis syndrome, the mean serum phosphorus level peaked at 7. Pui and colleagues 40 documented no increases in phosphorus levels and decreases in creatinine levels among patients who were at high risk for the tumor lysis syndrome and were treated with rasburicase.
At the time of the study, rasburicase was not available in the United States. Urinary alkalinization increases uric acid solubility but decreases calcium phosphate solubility Fig.
Because it is more difficult to correct hyperphosphatemia than hyperuricemia, urinary alkalinization should be avoided in patients with the tumor lysis syndrome, especially when rasburicase is available. In patients treated with rasburicase, blood samples for the measurement of the uric acid level must be placed on ice to prevent ex vivo breakdown of uric acid by rasburicase and thus a spuriously low level. Patients with glucosephosphate dehydrogenase deficiency should avoid rasburicase because hydrogen peroxide, a breakdown product of uric acid, can cause methemoglobinemia and, in severe cases, hemolytic anemia.
Hyperkalemia remains the most dangerous component of the tumor lysis syndrome because it can cause sudden death due to cardiac dysrhythmia. Patients should limit potassium and phosphorus intake during the risk period for the tumor lysis syndrome. Hemodialysis and hemofiltration effectively remove potassium. Glucose plus insulin or beta-agonists can be used as temporizing measures, and calcium gluconate may be used to reduce the risk of dysrhythmia while awaiting hemodialysis.
Hypocalcemia can also lead to life-threatening dysrhythmias and neuromuscular irritability; controlling the serum phosphorus level may prevent hypocalcemia. Symptomatic hypocalcemia should be treated with calcium at the lowest dose required to relieve symptoms, since the administration of excessive calcium increases the calcium—phosphate product and the rate of calcium phosphate crystallization, particularly if the product is greater than 60 mg 2 per square deciliter Fig.
Hypocalcemia not accompanied by signs or symptoms does not require treatment. Despite the lack of studies that show the efficacy of phosphate binders in patients with the tumor lysis syndrome, this treatment is typically given. The role of renal phosphate leak in renal lithiasis and the use of phosphate binders have recently been reviewed in the Journal.
Despite optimal care, severe acute kidney injury develops in some patients and requires renal replacement therapy Table 3 in the Supplementary Appendix. Although the indications for renal-replacement therapy in patients with the tumor lysis syndrome are similar to those in patients with other causes of acute kidney injury, somewhat lower thresholds are used for patients with the tumor lysis syndrome because of potentially rapid potassium release and accumulation, particularly in patients with oliguria.
In patients with the tumor lysis syndrome, hyperphosphatemia-induced symptomatic hypocalcemia may also warrant dialysis. Phosphate removal increases as treatment time increases, which has led some to advocate the use of continuous renal-replacement therapies in patients with the tumor lysis syndrome, including continuous venovenous hemofiltration, continuous venovenous hemodialysis, or continuous venovenous hemodiafiltration.
One study that compared phosphate levels among adults who had acute kidney injury that was treated with either conventional hemodialysis or continuous venovenous hemodiafiltration showed that continuous venovenous hemodiafiltration more effectively reduced phosphate.
Despite a potassium level of 5. Urine output is the key factor to monitor in patients who are at risk for the tumor lysis syndrome and in those in whom the syndrome has developed. In patients whose risk of clinical tumor lysis syndrome is non-negligible, urine output and fluid balance should be recorded and assessed frequently.
Patients at high risk should also receive intensive nursing care with continuous cardiac monitoring and the measurement of electrolytes, creatinine, and uric acid every 4 to 6 hours after the start of therapy. Those at intermediate risk should undergo laboratory monitoring every 8 to 12 hours, and those at low risk should undergo such monitoring daily.
Monitoring should continue over the entire period during which the patient is at risk for the tumor lysis syndrome, which depends on the therapeutic regimen. In a protocol for acute lymphoblastic leukemia, which featured up-front, single-agent methotrexate treatment, 53 new-onset tumor lysis syndrome developed in some patients at day 6 or day 7 of remission-induction therapy after the initiation of combination chemotherapy with prednisone, vincristine, and daunorubicin on day 5 and asparaginase on day 6.
Patients at high risk for the tumor lysis syndrome may also receive low-intensity initial therapy. Slower lysis of the cancer cells allows renal homeostatic mechanisms to clear metabolites before they accumulate and cause organ damage.
Similarly, many groups subscribe to a week of prednisone monotherapy for childhood acute lymphoblastic leukemia. Howard reports receiving consulting fees from EnzymeRx and Sanofi-Aventis. Disclosure forms provided by the authors are available with the full text of this article at NEJM. National Center for Biotechnology Information , U. N Engl J Med. Author manuscript; available in PMC Sep 9. Scott C. Howard , M.
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