A middle-aged woman with a history of leiomyosarcoma of the uterus treated with surgery and adjuvant chemotherapy suffered a bulky metastatic recurrence 1 year later. She elected treatment with palliative eribulin, presenting with acute renal failure and electrolyte abnormalities consistent with tumour lysis syndrome on cycle 1 day 8. Despite aggressive supportive care and treatment including intravenous hydration, bicarbonate and rasburicase, she continued to decline, ultimately foregoing haemodialysis in favour of palliative care and passed away in the hospital.

Tumour lysis syndrome (TLS) is a life-threatening complication wherein massive tumour cell lysis results in severe metabolic abnormalities. TLS generally follows chemotherapy of rapidly proliferating haematological malignancies; spontaneous TLS and TLS from treatment of solid tumours are infrequently reported. We present a rare case of TLS following treatment of a large gastrointestinal stromal tumour (GIST) in a 63- year-old man. Imatinib was started for tumour size reduction prior to surgical intervention and in 5 days the patient developed metabolic derangements consistent with TLS. Imatinib was held and fluids, allopurinol and rasburicase were started. All metabolic abnormalities resolved in 3 days. Imatinib was restarted, and he eventually underwent surgical intervention. This is the second case demonstrating successful reinitiation of imatinib following TLS when treating GIST. We highlight the importance of risk factor assessment and need for pre-emptive therapy to prevent TLS when using tyrosine kinase inhibitor therapy.

BACKGROUND: Data from low- and middle-income countries on tumor lysis syndrome (TLS) in the pediatric population are limited. This study aims to analyze the clinical and biochemical characteristics and treatment outcomes of TLS in children with leukemia/lymphomas in a resource-limited setting.
PROCEDURE: Children with intermediate risk (IRD) and high risk (HRD) for developing TLS were retrospectively studied at a tertiary cancer center in India.
RESULTS: Over a three-year period, 224 children with acute leukemia/lymphoma having IRD (21.8%, n = 49) and HRD (78.1%, n = 175) were identified. TLS developed in 53.6% (n = 120) cases, of which 75% (n = 90) had laboratory TLS alone. Thirteen children had clinical TLS (C-TLS) at presentation while 17 patients progressed to develop C-TLS. TLS developed in 51% (n = 25) and 54.5% (n = 95) of children with IRD and HRD, respectively. Rasburicase was used in 8.5% (n = 19) cases and five children required hemodialysis. Two children (0.8%) expired during the course of TLS management. Multivariate analysis identified the presence of hyperuricemia as the single significant risk factor for developing TLS. When children in whom a 25% change in biochemical values from the baseline that falls within the normal range were excluded, 21.4% (48/224) cases were identified to have clinically relevant TLS (8% in IRD and 25% in HRD).
CONCLUSION: With hydration, supportive care and judicious use of rasburicase, it is feasible to manage TLS efficiently in resource-limited settings. A modification of the TLS definition criteria would help to identify clinically relevant TLS.

Tumour lysis syndrome (TLS) is a rare oncological emergency in solid tumours. Because it is associated with bad short-term prognosis, early recognition and treatment are mandatory. This case refers to a middle-aged woman who presented with stage IV colon cancer, with massive hepatic involvement. After three cycles of first-line FOLFOX (folinic acid, 5-fluorouracil and oxaliplatin), she developed acute kidney injury and hyperkalaemia that did not respond to standard measures. High suspicion of TLS prompted further corroborating investigations and early intensive care unit admission. With vigorous hydration and allopurinol, TLS completely resolved and the patient was discharged. Prophylaxis of subsequent TLS recurrence was complicated by biopsy-proven neutrophilic vasculitis secondary to allopurinol. Prevention of TLS with hydration and rasburicase was performed prior to each subsequent cycle of chemotherapy. This case report is intended to highlight risk factors for TLS in solid tumours and focus on treatment and secondary prophylaxis of TLS.

Rasburicase is a novel drug used during the management of tumor lysis syndrome. In countries with limited resources, it is frequently given at a lower dose and only for the treatment of established tumor lysis syndrome and not as prophylaxis. A retrospective study was conducted in the department of pediatric oncology at a tertiary referral oncology center in south India to analyze the use of rasburicase over the past 3 years. Data of all the 18 children (< 14 years of age) who were given rasburicase for the management of hyperuricemia were collected and analyzed. With a mean rasburicase dose of 0.085 mg/kg, hyperuricemia was managed efficiently without the need for a hemodialysis in 16 children (88.8 %). The fall in mean serum uric acid levels after the administration of a single dose of rasburicase at 4, 24, and 48 hours was 31.18 %, 64.8 %, and 74.5 %, respectively. Rasburicase efficiently decreases the uric acid levels to a normal level within a short period. In resource-limited settings, rasburicase at a lower dose is a promising option for managing hyperuricemia in the event of a tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) is a life-threatening disorder that occurs mainly in patients with high-tumor burden hemato-oncologic malignancies. It results in metabolic derangements, including hyperuricemia and acute renal failure. The powerful management for TLS is a daily dose of rasburicase for up to 5 days before chemotherapy; however, the optimal dose and duration of rasburicase for TLS prophylaxis have not been standardized for patients at high risk for TLS. Therefore, we evaluated the efficacy of single-dose rasburicase for prophylactic purposes in patients with malignant lymphoma at high risk for TLS.
PATIENTS AND MATERIALS: We retrospectively evaluated patients with malignant lymphoma at high risk for TLS treated with a prophylactic single-dose of rasburicase (0.1-0.2 mg/kg) from March 2012 to March 2016.
RESULTS: A total of 67 patients treated with a single-dose of rasburicase for prophylaxis were analyzed. A relatively large number of patients (n = 23; 34.3%) had the highly proliferative lymphoblastic lymphoma subtype (n = 14) or Burkitt lymphoma (n = 9) and were at the highest risks of tumor lysis. Two patients were newly diagnosed with TLS; the incidence of TLS after single-dose prophylaxis was 3.0%. Multivariate analysis revealed no predictable risk factors for response to prophylactic rasburicase, though increased level of serum creatinine approached statistical significance in reducing the efficacy of single-dose rasburicase to prevent TLS (odds ratio, 3.61; P = .054).
CONCLUSION: Our data indicated that single-dose rasburicase effectively prevented progression of TLS, and, regardless of any risk factors, including increased creatinine, single-dose rasburicase for TLS prophylaxis was useful in patients with lymphoma at a high risk for TLS.

Tumor lysis syndrome (TLS) is a potentially fatal condition defined both by laboratory and clinical criteria. It is caused by the catabolism of tumor cells which leads to considerable release and elevated levels of phosphate, potassium and uric acid in the bloodstream. These electrolyte derangements predispose patients to renal tubule uric acid precipitation, acute kidney injury, arrhythmias, neuromuscular irritability and even seizures. Although this phenomenon is well described with hematological malignancies, it is also known to occur among solid tumors. We present a rare case of treatment-naïve spontaneous TLS that occurred in a 69-year-old male with metastatic prostate adenocarcinoma with hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, elevated liver enzymes, AKI and hemodynamic instability. Despite our best resuscitative efforts with intravenous hydration, electrolyte monitoring, Rasburicase and renal replacement therapy, the patient continued to decline, was made comfort care and expired shortly thereafter. Physicians encountering patients with the above presentation must entertain a diagnosis of TLS despite its rarity in solid tumors, as early diagnosis leads to timely treatment, thereby maximizing patients' chances at survival.

BACKGROUND: This case report describes a spontaneous tumor lysis syndrome due to a rare solid tumor.
CASE PRESENTATION: A 65-year-old white woman had tumor lysis syndrome, which represent a dangerous oncological emergency. This syndrome occurs usually with a hematological tumor, but in this case our patient had a solid tumor, which was a rare extraskeletal osteosarcoma, localized in her pelvic region. She also had lung metastases and bilateral hydronephrosis. After spontaneous tumor lysis syndrome, she had acute renal insufficiency, which was treated with hemodialysis and successively with rasburicase, Kayexalate (sodium polystyrene sulfonate), and febuxostat.
CONCLUSION: Tumor lysis syndrome represents an oncological emergency, which must be suspected and treated as soon as possible.

BACKGROUND: Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Previous reviews did not find clear evidence of benefit of urate oxidase in children with cancer. This review is the second update of a previously published Cochrane review.
OBJECTIVES: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies.
SEARCH METHODS: In March 2016 we searched CENTRAL, MEDLINE, Embase, and CINAHL. In addition, we searched the reference lists of all identified relevant papers, trials registers and other databases. We also screened conference proceedings and we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis.
SELECTION CRITERIA: Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data.
MAIN RESULTS: We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. No new studies were identified in the update. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT did not evaluate the primary outcome (incidence of clinical TLS). It showed no clear evidence of a difference in mortality (both all-cause mortality (Fisher's exact test P = 0.23) and mortality due to TLS (no deaths in either group)), renal failure (Fisher's exact test P = 0.46), and adverse effects between the treatment and the control groups (Fisher's exact test P = 1.0). The frequency of normalisation of uric acid at four hours (10 out of 10 participants in the treatment group versus zero out of nine participants in the control group, Fisher's exact test P < 0.001) and area under the curve of uric acid at four days (MD -201.00 mg/dLhr, 95% CI -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group.One CCT evaluated the primary outcome; no clear evidence of a difference was identified between the treatment and the control groups (RR 0.77, 95% CI 0.44 to 1.33; P = 0.34). Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); no clear evidence of a difference in all-cause mortality was identified between the groups (RR 0.19, 95% CI 0.01 to 3.42; P = 0.26). Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs: MD -3.80 mg/dL, 95% CI -7.37 mg/dL to -0.24 mg/dL; P = 0.04), three days (two CCTs: MD -3.13 mg/dL, 95% CI -6.12 mg/dL to -0.14 mg/dL; P = 0.04), four days (two CCTs: MD -4.60 mg/dL, 95% CI -6.39 mg/dL to -2.81 mg/dL; P < 0.00001), and seven days (one CCT: MD -1.74 mg/dL, 95% CI -3.01 mg/dL to -0.47 mg/dL; P = 0.007) after therapy, but not one day (three CCTs: MD -3.00 mg/dL, 95% CI -7.61 mg/dL to 1.60 mg/dL; P = 0.2), five days (one CCT: MD -1.02 mg/dL, 95% CI -2.24 mg/dL to 0.20 mg/dL; P = 0.1), and 12 days (one CCT: MD -0.80 mg/dL, 95% CI -2.51 mg/dL to 0.91 mg/dL; P = 0.36) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03).Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg). The primary outcome was not evaluated. No clear evidence of a difference in mortality (all-cause mortality (Fisher's exact test P = 1.0) and mortality due to TLS (no deaths in both groups)) and renal failure (no renal failure in both groups) was identified. It demonstrated no clear evidence of a difference in uric acid normalisation (RR 1.07, 95% CI 0.89 to 1.28; P = 0.49) and uric acid level at four hours (MD 8.10%, 95% CI -0.99% to 17.19%; P = 0.08). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no clear evidence of a difference between treatment groups was identified (RR 0.54, 95% CI 0.12 to 2.48; P = 0.42).The quality of evidence ranks from very low to low because of imprecise results, and all included trials were highly susceptible to biases.
AUTHORS' CONCLUSIONS: Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical TLS, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

CASE REPORT: We report on a male patient with Tuberous Sclerosis Complex (TSC), which was prenatally diagnosed. At the age of 3 months the patient developed acute renal failure with excessive hyperuricemia. Kidney function improved after rehydration and application of rasburicase, however without full recovery. Due to the inappropriate high levels of uric acid compared to kidney function, screening of hypoxanthine-guanine phosphoribosyltransferase (HPRT) related diseases was initiated. Mutation analysis revealed a deletion of exon 2 and 3 of the HPRT gene confirming the diagnosis of Lesch-Nyhan Disease (LND). After initiation of allopurinol therapy renal function further improved. In the following months the patient developed clinically a typical neurological phenotype of LND and TSC with seizures, severe dystonia and developmental delay.
CONCLUSION: Acute renal failure is a rare complication of HPRT related diseases. Combination of two inherited diseases may lead to a delayed diagnosis due to a mixed and maybe misleading phenotype.

BACKGROUND: Tumor lysis syndrome (TLS) is a potentially fatal complication in patients with large, rapidly proliferating tumor cell cancers that may occur after chemotherapy. Patients with TLS are complicated to treat and often have an unpredictable trajectory.
OBJECTIVES: The purpose of this article is to report two cases with unusual clinical manifestations and unexpected outcomes during cancer treatment and to share best practices for this situation.
METHODS: The authors described details from two unusual cases and outlined lessons learned. The authors described a newly developed clinical order set (protocol) to support optimal care for patients at risk for TLS.
FINDINGS: Implementing best practices, the order set prompts early identification of TLS risk and provides step-by-step guidance to eliminate or control TLS.

A 78-year-old man, with a 6-year history of stable chronic myelomonocytic leukaemia (CMML), presented with general deterioration and worsening pancytopenia. Bone marrow biopsy showed that his disease had transformed into acute myeloid leukaemia (AML). He was started on a supportive transfusion regimen and did not receive any chemotherapy or corticosteroids. Several weeks later, he developed acute renal failure and was admitted to a medical admissions ward. Spontaneous tumour lysis syndrome (sTLS, grade 1) was diagnosed, as per the Cairo and Bishop criteria. He was treated with intravenous fluids, rasburicase and allopurinol. His renal function improved and he recovered from the sTLS. The authors believe that this is the first published case of sTLS occurring as a result of CMML transforming into AML; it highlights the importance of recognising sTLS as a cause of renal failure and electrolyte disturbance before cancer treatment begins.

OPINION STATEMENT: Hyperleukocytosis has a high morbidity index. The involvement of the respiratory or central nervous system and the metabolic derangements accompanying tumor lysis are responsible for early mortality. Standard care for acute hyperleukocytosis must include cytoreduction, proper supportive care, and prevention of tumor lysis. Hydration, alkalization, allopurinol, or urate oxidase should be started immediately. In patients with low platelet count of less than 20,000/mm(3), platelet transfusions should be given to prevent cerebral hemorrhage, as platelets do not add substantially to blood viscosity. Packed red blood cells must be given with caution as they can significantly increase blood viscosity. If the patient is hemodynamically stable, packed red transfusions should be planned when the hemoglobin level is less than 7-8 g/dl, avoiding post-transfusional levels above 10 g/dl. Coagulation abnormalities should be corrected. Leukapheresis has been advocated to correct metabolic abnormalities and to decrease viscosity by reducing the peripheral white blood count. However, leukapheresis may fail to decrease the leukocyte count substantially or may achieve only a transient tumor bulk reduction. The procedure is generally well tolerated but can involve problems such as the need for anticoagulation or difficulty of access, and limited availability in many institutions.Specific antileukemic therapy must be initiated as soon as life-threatening complications have been corrected as it remains the first-line treatment of hyperleukocytosis.

A 25-year-old man was admitted to our hospital complaining of right scrotal pain and upper abdominal pain. A computed tomographic scan indicated a right scrotal mass, a huge liver mass, and multiple lung masses, although there was no enlarged retroperitoneal lymph node swelling. Laboratory tests showed severe liver and kidney dysfunction and high levels of serum α-fetoprotein (11,997 ng/ml). Although needle biopsies of the testicular and liver masses were performed, the tissues were insufficient for a pathological diagnosis. As liver and kidney function worsened, we started chemotherapy with bleomycin, etoposide, and cisplatin (BEP chemotherapy), which was modified because of the liver and renal dysfunction. We also used continuous hemodiafiltration and rasburicase to prevent tumor lysis syndrome. After induction of chemotherapy, the liver and kidney dysfunction improved immediately and the high orchiectomy was performed on day 8 after chemotherapy. The pathological diagnosis was a yolk sac tumor. He underwent four courses of the BEP regimen and five courses of the TIN regimen (paclitaxel, ifosphamide, and nedaplatin), followed by the resection of liver metastases. There was no evidence of viable cells in the resected liver and no recurrence was evident at 1 year postoperatively.

Spontaneous tumor lysis syndrome is a rare initial presentation of hematologic malignancy in children that typically presents with complications of electrolyte derangement, specifically hyperkalemia, hyperphosphatemia, and hyperuricemia. We report a case of a 5-year-old boy who presented to the emergency department with gross hematuria, abdominal pain, and vomiting and was ultimately diagnosed with uric acid nephrolithiasis and acute renal failure secondary to spontaneous tumor lysis syndrome in the setting of T-cell acute lymphoblastic leukemia. Tumor lysis syndrome is considered an oncologic emergency, and in this case, the child required urgent treatment with potassium-binding agents, rasburicase, and hemodialysis. This case demonstrates that occult hematologic malignancy should be suspected in cases of nephrolithiasis and acute renal failure when found in conjunction with hyperuricemia despite a normal complete blood count at the time of presentation.

Tumor lysis syndrome (TLS) is a rare but potentially life-threatening complication of neoplasms, preferentially hematological malignancies. Well known since at least ninety years ago, this condition can be misdiagnosed and incorrectly managed due to rapid onset of symptoms, sometimes overlapping with cancer-derived clinical conditions. Our purpose is to discuss some old and new issues of this syndrome. Predisposing factors as type of malignancy, chemotherapy regimen and age are promptly available and useful tools for inducing TLS suspicion. Management of clinical syndrome requires hydration, fluid balance, electrolytes and hyperuricemia correction, and ultimately dialysis when acute kidney injury is worsening.

BACKGROUND: Rasburicase is a recombinant urate oxidase enzyme that converts uric acid to allantoin (an inactive and soluble metabolite that is readily excreted in urine). It is used for the management of tumor lysis syndrome (TLS) in cancer patients receiving chemotherapy. Although rasburicase is a generally safe and effective treatment, it can be associated with the rare and potentially severe complication of methemoglobinemia. Here, we report a case of rasburicase-induced methemoglobinemia in a patient who was diagnosed with aggressive non-Hodgkin's lymphoma.
CASE REPORT: A 74-year-old man with aggressive non-Hodgkin's lymphoma was admitted for initiation of chemotherapy. Upon admission, the patient was found to have hyperkalemia, hyperuricemia, hyperphosphatemia, elevated LDH levels, and acute renal failure. As a result, he was diagnosed with TLS. Rasburicase 6 mg was administered intravenously over a period of 30 min to treat TLS. Later, methemoglobinemia developed, with requirements for oxygen supplementation. Multiple units of packed red blood cells were transfused for recurrent significant anemia secondary to his cancer co-morbidity. The patient was tested for glucose-6 phosphate dehydrogenase (G6PD) deficiency, which returned negative; therefore, methylene blue was considered. After transfusion, the methemoglobin level normalized over the course of a few days, and the oxygen saturation improved without the use of methylene blue. However, during his hospitalization, the patient also developed a pulmonary embolism and had evidence of acute coronary syndrome. Later, the patient died of multiple complications related to his cancer co-morbidity on day 12 of admission.
CONCLUSIONS: Blood transfusion and supplemental oxygen, without the use of methylene blue, may be an appropriate therapeutic alternative in rasburicase-induced methemoglobinemia treatment.

PATIENT: 9-year-old African American male.
CHIEF COMPLAINT: Recently diagnosed with acute lymphoblastic leukemia (ALL) after investigation into a large anterior mediastinal mass causing airway compression.
HISTORY OF PRESENT ILLNESS: The day before the unexpected urgent glucose-6-phosphate dehydrogenase (G6PD) request, the patient was diagnosed with an aggressive form of leukemia and a significant tumor mass causing airway compression. A computed tomography (CT) scan indicated potential renal involvement. Based on this information and the size of the mass, the patient was referred for immediate chemotherapy. However, there was a concern that he could develop tumor lysis syndrome (TLS) during treatment. To avoid this condition, the pediatric intensive care unit (ICU) sought to pretreat the child with rasburicase, which led to the emergency G6PD request.
PREVIOUS MEDICAL HISTORY: Unknown.
FAMILY HISTORY: Largely unknown, but no apparent chronic diseases.
PHYSICAL EXAMINATION FINDINGS: Three weeks of progressively worsening lymphadenopathy, coughing, night sweats, mild hepatosplenomegaly, and breathing difficulty when supine. The patient arrived at the medical center for airway management and had a temperature of 36.1°C; blood pressure, 120/87 mmHg; pulse, 115 bpm; respiratory rate, 22 breaths per minute, with labored breathing but normal O(2) saturation while upright and awake, in room air.
PRINCIPLE LABORATORY FINDINGS: Table 1.

A 56-year-old woman with a new diagnosis of metastatic pancreatic cancer presents to the emergency room with generalised fatigue. The patient is afebrile, however, hypotensive and tachycardic. Physical examination shows diffuse lymphadenopathy. Initial laboratory tests indicate that the patient has hyperkalaemia, hypocalcaemia, with a high lactate dehydrogenase and high uric acid. The patient was also in renal failure. On the basis of the clinical presentation, the patient was diagnosed with spontaneous tumour lysis syndrome, despite the syndrome never having been reported in metastatic pancreatic cancer. The patient was treated appropriately with intravenous hydration, allopurinol and rasburicase. All laboratory abnormalities were corrected by day 3 of treatment.

OBJECTIVE: To define the efficacy and safety of low-dose rasburicase in children from south India with hematologic malignancies.
METHODS: This study is a retrospective analysis of data on 41 children with hematologic malignacies with laboratory evidence of tumor lysis syndrome (TLS) or clinical features indicating high risk for developing TLS. Patients were treated with rasburicase in doses of 0.1-0.15 mg/kg dose, repeated when necessary.
RESULTS: Male : Female ratio was 32:9. Thirty-six children had laboratory evidence of TLS and 5 were at risk for TLS. Diagnoses were T-cell acute lymphoblastic leukemia (ALL), 19; Pre-B ALL, 17; B-non-Hodgkin lymphoma (NHL), 2; T-NHL, 2; and acute myeloid leukemia (AML), 1. Initial plasma uric acid (PUA): median, 8.5 mg/dl (range, 4.3 to 45.5). Six had creatinine levels of >2 mg/dl on admission; and 10 had peak PO4 levels of >10 mg/dl. Dose of rasburicase used: median, 0.12 mg/kg (range, 0.08-0.24). Median reduction of PUA at 6 h: 80 % (range 40 to 98 %). Twenty-seven needed only one dose; 12 needed 2 or 3 doses; and two needed 5 doses each. One child required dialysis. None of the children developed anaphylaxis or hemolysis and there were no deaths from TLS.
CONCLUSIONS: Low-dose rasburicase (0.1-0.15 mg/kg) is safe and effective in reducing PUA in Indian children with lymphoid malignancies, and thus it may reduce the risk of renal failure from TLS.

BACKGROUND: Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is effective in reducing serum uric acid, the build-up of which causes TLS. It is uncertain whether high-quality evidence exists to support its routine use in children with malignancies.
OBJECTIVES: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies.
SEARCH METHODS: This is an update of the original review. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library issue 1, 2013), MEDLINE (1966 to February 2013), Embase (1980 to February 2013), and CINAHL (1982 to February 2013). In addition, we searched the reference lists of all identified relevant papers. We also explored other internet sources (updated search on 26 February 2013): the NHS' National Research Register, the US National Institutes of Health Ongoing Trials Register, the metaRegister of Controlled Trials, and ProQuest Dissertations & Theses Database. We also screened conference proceedings of the American Society of Clinical Oncology, the European Society for Medical Oncology, and the International Society of Paediatric Oncology meetings from 1993 to 2012. Finally, we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis.
SELECTION CRITERIA: Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data.
MAIN RESULTS: We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT showed no significant difference in mortality (both all-cause mortality and mortality due to TLS), renal failure, and adverse effects between the treatment and the control groups. The frequency of normalisation of uric acid at four hours (Fisher's exact test P < 0.001) and area under curve of uric acid at four days (MD -201.00 mg/dLhr, 95% confidence interval (CI) -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group. The trial did not evaluate the primary outcome (incidence of clinical TLS).Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); all-cause mortality was not significantly different between the groups. Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs), three days (two CCTs), four days (two CCTs), and seven days (one CCT) after therapy, but not one day (three CCTs), five days (one CCT), and 12 days (one CCT) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03). One CCT evaluated the primary outcome; no significant difference was identified.Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated no significant difference in uric acid normalisation and uric acid level at four hours). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no significant difference between treatment groups was identified. No significant difference in mortality (all-cause mortality and mortality due to TLS) and renal failure was identified. The primary outcome was not evaluated.All included trials were highly susceptible to biases.
AUTHORS' CONCLUSIONS: Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical tumour lysis syndrome, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

BACKGROUND: Patients with hematological malignancies that are highly proliferative and have high tumor burden are at high risk of developing hyperuricemia and tumor lysis syndrome (TLS), spontaneously and while undergoing chemotherapy.
AIM: To assess the safety and efficacy of a new generic formulation of recombinant rasburicase in prevention and treatment of malignancy-associated hyperuricemia.
MATERIALS AND METHODS: An open-label, multicenter, phase-III study was conducted on 100 eligible patients with high risk for TLS. Rasburicase was administered 0.2 mg/kg intravenously over 30 min, daily, for 4 days. The outcome measures were percentage of reduction in plasma uric acid at 4 h after rasburicase, plasma uric acid area under the curve (AUC)(0-96 h) and incidence of adverse events.
RESULTS: Eighty eight patients completed the study period of 10 days. After rasburicase administration, there was a 75.3 ± 28.5% of reduction in plasma uric acid at 4 h as compared to baseline. The plasma uric acid AUC(0-96 h) was 259.9 ± 215.5 mg/dL h. Safety of rasburicase was assessed on the basis of changes in vitals, hematological, and biochemical parameters from baseline to termination. Except for the plasma uric acid level, there was no significant difference in any of the parameters. Mild to moderate adverse events were reported in 29 patients. Three patients had serious adverse events (SAEs) unrelated to rasburicase.
CONCLUSIONS: These results demonstrated that recombinant rasburicase that is indigenously developed is effective for prevention and management of hyperuricemia in patients who are at high risk of developing TLS.

Tumor lysis syndrome (TLS) is a potentially fatal complication of induction therapy for several types of malignancies. Electrolyte derangements and even downstream complications may also occur prior to the initial presentation to a medical provider, before an oncologic diagnosis has been established. It is therefore imperative that emergency physicians be familiar with the risk factors for TLS in children as well as the criteria for diagnosis and the strategies for prevention and management. Careful evaluation of serum electrolytes, uric acid, and renal function must occur. Patients at risk for TLS and those who already exhibit laboratory or clinical evidence of TLS require close monitoring, aggressive hydration, and appropriate medical treatment.

We describe a case of a 73-year-old man who presented with right-sided abdominal pain associated with palpable mass. Initial laboratory examination was normal except lactate dehydrogenase level. Subsequent CT image showed situs inversus and splenic mass with multiple lymph nodes enlargement. Biopsy taken from the splenic mass demonstrated mantle cell lymphoma. Staging CT examination was performed with intravenous contrast, and patient developed altered mental status, respiratory failure and acute kidney injury requiring intensive care unit care. Laboratory examination revealed hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia, which are consistent with spontaneous tumour lysis syndrome. The patient was successfully treated with rasburicase and haemodialysis, and completed the first course of chemotherapy without further complications.

Multiple myeloma is the second most common type of hematologic malignancy. It is a B-cell malignancy that affects the bone marrow and often results in thrombocytopenia as well as renal dysfunction. Treatment options range from oral and intravenous chemotherapy to bone marrow transplantation and supportive care. Carfilzomib was approved by the U.S. Food and Drug Administration in 2012 as a treatment option for patients with refractory multiple myeloma who have received at least two previous therapies and have demonstrated recent disease progression. According to the product labeling, the frequency of tumor lysis syndrome (TLS) is less than 1% in patients treated with carfilzomib. To our knowledge, no postmarketing events of TLS have been reported or published. We describe a 55-year-old man with relapsed multiple myeloma who developed a case of TLS that occurred after he received his first two doses of carfilzomib therapy on days 1 and 2; he also had chronic kidney disease secondary to his neoplastic disease. Beginning on day 4, his uric acid levels spiked to critical levels, prompting the use of rasburicase, which returned the levels to within normal limits. His phosphorus and creatinine levels increased during days 5 and 6. On day 8, the patient died, likely due to a combination of disease progression and the adverse effects of treatment. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's development of TLS and carfilzomib therapy. The Hill criteria were used as a secondary measure to ensure causality, which also suggested a link between the patient's development of TLS and the administration of carfilzomib. This case report shows that even the most unlikely of adverse events may occur with medications, especially in the case of a new or recently approved medication. Caution must be taken when deciding to treat and when choosing hydration and premedications with regard to biologic and chemotherapeutic medications. In this case, additional hydration may have been considered. Although given the extent of the adverse reaction combined with the patient's underlying renal dysfunction, extra fluid may or may not have proven beneficial. The use of prophylactic rasburicase or allopurinol could have been considered, but these measures are not typically used with multiple myeloma due to the low incidence of TLS. All things considered, this unlikely adverse reaction may occur in certain patients. If other cases such as this occur, it may be advisable to use TLS prophylaxis in the future in certain patient populations, including those with renal dysfunction or worsening disease states.

The authors evaluated complications in pediatric acute leukemia with "very high" leukocytosis (VHL) prior to rasburicase availability and without leukopheresis. From Jun 2003 through Dec 2009, 45 out of 457 (10 %) pediatric acute leukemia patients had VHL. Median WBC for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients was 296,500/mm3 (200,000-615,220) and 206,300/mm3 (106,100-541,900) respectively. Laboratory and clinical tumor-lysis-syndrome was seen in 37.7 % and 13.3 % patients respectively; none required dialysis; 6.6 % died due to CNS/pulmonary bleed. Thrombocytopenia <31,000/mm3 was associated with hypocalcemia (p = 0.04) and mortality (p = 0.04), and hypoalbuminemia with kidney dysfunction (p = 0.04). In resource-limited setting, VHL patients with thrombocytopenia may warrant rasburicase with or without leukopheresis, and aggressive platelet support.

Laboratory (LTLS) and clinical (CTLS) tumour lysis syndrome (TLS) are frequent complications in newly diagnosed children with advanced mature B cell non-Hodgkin lymphoma (B-NHL). Rasburicase, compared to allopurinol, results in more rapid reduction of uric acid in paediatric patients at risk for TLS. However, the safety and efficacy of rasburicase for the treatment or or prevention of TLS has not been prospectively evaluated. Children with newly diagnosed stage III-IV, bone marrow(+) and/or central nervous system(+) mature B-NHL received hydration and rasburicase prior to cytoreductive therapy. Rasburicase was safe and well-tolerated and there were no grade III-IV toxicities probably or directly related to rasburicase. Patients with an initial lactate dehydrogenase ≥2× upper limit of normal had a significantly elevated uric acid level (P = 0·005), increased incidence of TLS (P-0·005) and lower glomerular filtration rate (GFR; P < 0·001). Following rasburicase, there was only a 9% and 5% incidence of LTLS and CTLS, respectively. Furthermore, there was a significant improvement in estimated GFR from Day 0 to Day 7 following rasburicase (P = 0·0007) and only 1·3% of patients required new onset renal assisted support after rasburicase administration. A TLS strategy incorporating rasburicase prior to cytoreductive chemotherapy proved safe and effective in preventing new onset renal failure and was associated with a significant improvement in GFR.

In tumour lysis syndrome (TLS), metabolic alterations caused by the destruction of malignant cells manifest as laboratory abnormalities with (clinical TLS) or without (laboratory TLS) organ dysfunction. This prospective multicentre cohort study included 153 consecutive patients with malignancies at high risk for TLS (median age 54 years (interquartile range, 38-66). Underlying malignancies were acute leukaemia (58%), aggressive non-Hodgkin lymphoma (29.5%), and Burkitt leukaemia/lymphoma (12.5%). Laboratory TLS developed in 17 (11.1%) patients and clinical TLS with acute kidney injury (AKI) in 30 (19.6%) patients. After adjustment for confounders, admission phosphates level (odds ratio [OR] per mmol/l, 5.3; 95% confidence interval [95% CI], 1.5-18.3), lactic dehydrogenase (OR per x normal, 1.1; 95%CI, 1.005-1.25), and disseminated intravascular coagulation (OR, 4.1; 95%CI, 1.4-12.3) were associated with clinical TLS; and TLS was associated with day-90 mortality (OR, 2.45; 95%CI, 1.09-5.50; P = 0.03). In this study, TLS occurred in 30.7% of high-risk patients. One third of all patients experienced AKI, for which TLS was an independent risk factor. TLS was associated with increased mortality, indicating a need for interventional studies aimed at decreasing early TLS-related deaths in this setting.

OBJECTIVE: To report a case of huge hepatocellular carcinoma associated with tumor lysis syndrome and its management.
CLINICAL PRESENTATION AND INTERVENTION: A 51-year-old hepatitis B carrier visited our clinic with progressive weight loss over recent months. Abdominal ultrasonography and magnetic resonance imaging revealed a huge hepatic mass in a cirrhotic liver, identified as hepatocellular carcinoma. A hepatologist and surgeon recommended transarterial chemoembolization followed by hepatectomy. The patient underwent the procedure, with the complication of tumor lysis syndrome. He was treated with a single high dose (9 mg) of rasburicase and his clinical condition improved dramatically, with acute kidney injury subsiding without emergent hemodialysis.
CONCLUSIONS: This was a case of hepatocellular carcinoma with tumor lysis syndrome and acute kidney injury, treated successfully with rasburicase.

OBJECTIVES: To provide an up-to-date review of current literature on the pathophysiology, diagnosis, and management of five key malignancy-related complications: superior vena cava syndrome, malignant pericardial effusion, malignant spinal cord compression, hypercalcemia, and acute tumor lysis syndrome.
DATA SOURCES: Database searches and review of relevant medical literature.
DATA SYNTHESIS: Malignancy-related complications demand increased attention from intensivists due to their frequency and increasing cancer prevalence. Although such complications portend a poor prognosis, proper acute management can improve short-term outcomes by facilitating either definitive care of the underlying malignancy or the institution of appropriate palliative measures.
CONCLUSIONS: Knowledge of malignancy-induced complications in critically ill patients expedites the ability of the intensivist to properly manage them. Five complications commonly requiring emergency management are addressed in this review. Specifically, superior vena cava syndrome may warrant radiation, chemotherapy, vascular stenting, or surgical resection. Malignant pericardial effusion may require emergency pericardiocentesis if cardiac tamponade develops. Malignant spinal cord compression demands immediate spinal imaging, glucocorticoids, and either surgery or radiation. Hypercalcemia requires aggressive intravenous hydration and a bisphosphonate. Acute tumor lysis syndrome necessitates intravenous hydration, rasburicase, and management of associated electrolyte abnormalities.