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Background: Tumor lysis syndrome (TLS) is an oncologic emergency commonly seen in children with hemato-lymphoid malignancies. Recombinant urate oxidase (RUO) is used in both the prophylaxis and treatment of TLS. However, in resource-constrained countries, its role is mostly limited to the treatment of established TLS and data regarding the use of RUO and its outcome is sparse., Objective: To describe the outcome of Pediatric TLS following the use of a fixed - dose of RUO., Methods: A retrospective chart review of all children <15 years of age admitted in the Department of Paediatric Oncology, Kidwai Cancer Institute from April 2017 to July 2018 with TLS and treated with a single, fixed - dose (1.5 mg) RUO was undertaken., Results: During the study period, 255 children with hemato-lymphoid malignancies were diagnosed to be at risk of developing TLS. Of these, only 22 (8.6%) children developed TLS and received RUO. Among those with TLS, 15 (68.2%) had Acute Lymphoblastic Leukemia (ALL) while 7 (31.8%) had Non - Hodgkin lymphoma (NHL). 91% (20/22) children had spontaneous TLS and the remainder developed therapy-related TLS. Median age at presentation was 8 years (IQR 5.25,1.75) with 4.5:1 male: female ratio. The mean urate level at admission was 19.12 mg/dl (+/- 8mg/dl) (Range: 10.7-34.5). 91% (20/22) children received RUO at less than 0.15 mg/kg and the median dose of RUO was 0.05 mg/kg (IQR 0.038-0.08). Of the 22 children with TLS, 2 children failed to achieve normal serum urate levels at 24 hours in response to a single fixed-dose of RUO and hence received an extra dose of RUO. Serum urate levels remarkably declined following RUO administration from 19.12 mg/dl (+/-8) to 8.2 mg/dl (+/-3.9), 3.99 mg/dl (+/-1.6) and 2.84 mg/dl (+/-1.3) at 12h, 24h and 48h respectively. AKI was present in 15 (68.2%) children. The median eGFR of the group at diagnosis was 49 ml/min/1.73m2 (IQR 26.3, 70). None of the children required hemodialysis. No significant adverse events occurred., Conclusion: Fixed-dose RUO can achieve rapid, adequate and sustained drop in serum urate levels in Paediatric TLS. It is a useful strategy for managing TLS in resource-constrained settings.

Tumor lysis syndrome is a potentially lethal complication of chemotherapy, usually associated with aggressive hematologic malignancies. We describe the case of a young patient with metastatic hepatocellular cancer who developed rapid and fatal tumor lysis syndrome following initiation of sorafenib therapy. Although rare with sorafenib therapy for hepatocellular carcinoma, tumor lysis syndrome is serious complication. Patients with a high burden of disease at therapy initiation should have their metabolic parameters measured prior to starting therapy and closely followed for the first 1-2 weeks while being treated., (Copyright © 2018 King Faisal Specialist Hospital & Research Centre. All rights reserved.)

Multiple myeloma (MM) is a slow-growing malignancy characterized by a low proliferation rate of plasma cells and a relatively rare incidence of tumour lysis syndrome (TLS). Three myeloma patients developed TLS following cytotoxic therapy (two after radiation treatment) that was associated with an abrupt increase of serum free light chains (FLC). All three patients demonstrated extramedullary plasmacytomas that exhibited aggressive features compared to the original myeloma. The findings suggested that an abrupt liberation (rather than slow secretion) of FLC from myeloma cells may trigger a fulminant cast nephropathy and present an unrecognized risk factor and potentially aggravating component of TLS., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Tumour lysis syndrome (TLS) is a significant complication of haematologic malignancies and their management. The syndrome consists of laboratory abnormalities either alone (laboratory TLS) or with clinical sequelae including renal failure, seizures, and arrhythmias (clinical TLS). Clinical TLS is a predictor for worse overall morbidity and mortality in cancer patients, but can be prevented. Thus, accurate prognostication is critical to appropriate management of patients at risk for TLS, and incorporates both disease factors (tumour type and burden) and patient factors (baseline renal insufficiency or hyperuricaemia). Strategies to prevent TLS include hydration and allopurinol in low- and intermediate-risk patients and rasburicase in high-risk patients., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Myocardial calcification, a rare disease that leads to chronic or acute heart failure and with a poor prognosis, occurs in patients with abnormal calcium-phosphorus metabolism. The association between myocardial calcification and tumor lysis syndrome has not been reported to date. A 50-year-old man with hyperthermia and general malaise presented to our hospital and was clinically diagnosed with B-lymphoblastic leukemia (B-ALL) and febrile neutropenia accompanied by septic shock. Prednisolone was administered for tumor reduction. Two to three hours later, electrocardiography demonstrated ST elevation in V4-6, and blood tests showed elevated levels of cardiac enzymes. Transthoracic echocardiogram revealed diffuse severe hypokinesis with decreased left ventricular ejection fraction. Additionally, blood tests showed that serum phosphorus level increased to 8.0 mg/dl, which was likely due to tumor lysis syndrome. Circulatory and respiratory failure due to left heart failure progressed, and he died 3 days after administration of prednisolone. Pathological autopsy revealed diffuse proliferation of atypical B-lymphoblasts in the bone marrow, which led to the pathological diagnosis of B-ALL, accompanied by necrosis. On the cut surface of the heart, the left ventricle was dilated, and patchy yellowish-brown areas were present in the epicardial-side of the myocardium and spread through the circumferential wall of the left ventricle and interventricular septum. Microscopically, myocardial fibers were granularly basophilic in that area and were revealed as calcium deposits by Von Kossa staining. He was diagnosed with myocardial calcification. The drastic increase in the serum phosphorus level caused by tumor lysis syndrome seemed to be associated with myocardial calcification., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Early administration of rasburicase to enhance uric acid (UA) elimination has been adopted without robust evidence in support of its impact on clinical outcomes in tumor lysis syndrome (TLS), specifically, the prevention of acute kidney injury (AKI). This was a retrospective cohort study of adult lymphoma patients at intermediate or high risk for TLS. Excluded patients had AKI or were on dialysis at hospital admission. The incidence of new AKI in the setting of TLS was described along with predictors of its development, including early rasburicase use. In 383 included patients, the incidence of new-onset AKI during hospitalization was 6%. Predictors included age, history of renal or cardiovascular disease, and UA >8 mg/dL. Rasburicase use did not significantly impact the risk of developing AKI (HR 2.3; p  = .11). The UA level at the time of administration did not modify the effect of rasburicase on prevention of AKI ( p  = .36 for the interaction term).

What Is Known and Objective: Tumour lysis syndrome is an oncological emergency, characterized by rapid cytolysis leading to an abrupt rise of serum uric acid levels. The aim of the present meta-analysis is to evaluate the efficacy and safety of febuxostat as a preventive measure in patients at risk of tumour lysis syndrome development, by comparing it with allopurinol administration., Methods: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar databases were searched from inception to 15 December 2018. All studies evaluating the effectiveness of febuxostat in preventing tumour lysis syndrome were held eligible., Results and Discussion: Six studies were included with a total of 658 patients. Compared to allopurinol, febuxostat achieved a similar response rate (OR: 1.39, 95% CI: [0.55, 3.51]) and tumour lysis syndrome incidence (OR: 1.01, 95% CI: [0.56, 1.81]). Serum uric acid levels did not differ between the investigated groups at the second (MD: -0.21 mg/dL, 95% CI: [-1.30, 0.88]) and seventh (MD: -0.43 mg/dL, 95% CI: [-1.38, 0.51]) day of treatment. Elevation of liver function tests was the most common adverse effect, although its incidence was similar among patients treated with allopurinol and febuxostat., What Is New and Conclusions: The present meta-analysis suggests that febuxostat may serve as an effective alternative to allopurinol in the prevention of tumour lysis syndrome. Future large-scale studies should define the optimal febuxostat dosage, explore the most appropriate population for its administration and better define its safety profile., (© 2019 John Wiley & Sons Ltd.)

Purpose There is a lack of high-level evidence identifying meaningful outcomes and the optimal place in therapy of rasburicase in patients with, or at high risk for tumor lysis syndrome. The primary objective of this study was to evaluate and characterize outcomes resulting from an institution-specific guideline emphasizing supportive care, xanthine oxidase inhibitors, and lower doses of rasburicase. Methods In this retrospective chart review, we compared conservative rasburicase dosing, in accordance with newly developed UMHS tumor lysis syndrome guidelines, with aggressive rasburicase in adult patients (≥ 18 years of age) with hematological or solid tumor malignancies, and a uric acid level between 8 and 15 mg/dL. The primary efficacy outcome assessed the difference in the proportion of patients achieving a uric acid level <8 mg/dL within 48 h using a one-sided noninferiority test. The principle safety outcomes analyzed included incidence of acute kidney injury and hemodialysis requirement. Results One hundred sixty-one patients met inclusion criteria and were included in the study. Within 48 h of an elevated uric acid level, treatment was successful in 97.03% of patients in the conservative group, as compared with 98.33% in the aggressive group (difference, 1.3 percentage points; 95% confidence interval [CI], -3.33 to 5.93). Furthermore, there was no difference in the proportion of patients requiring hemodialysis (2.97% vs. 10.0%, p-value 0.079), or incidence of acute kidney injury (4.0% vs. 12.5%, p-value 1.00) between the treatment group and control group, respectively. Conclusions Conservative rasburicase use was noninferior to aggressive rasburicase use in patients with or at high risk for tumor lysis syndrome.

Aim: The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies., Patients and Methods: A retrospective analysis was performed in 45 pediatric patients with hematological malignancies who received febuxostat (10 mg daily, n=20) or allopurinol (300 mg/m 2 daily, n=25) as a prophylaxis for TLS., Results: A significant decrease of serum uric acid (UA) level was observed in patients with febuxostat over the first 2 days (6.6±3.8 mg/dl vs. 4.5±2.8 mg/dl, p<0.001). The febuxostat group also showed significant reduction of urinary UA/creatinine ratios during the first two days of treatment (0.98±0.85 vs. 0.51±0.26, p=0.010). No significant differences were observed between febuxostat-treated and allopurinol-treated patients regarding the percent change in serum UA level., Conclusion: Febuxostat had a notable effect in reducing serum UA level in children with hematological malignancies., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan., Methods: An allopurinol-controlled multicenter, open-label, randomized, parallel-group comparative study was carried out. Patients with malignant tumors receiving chemotherapy, who had an intermediate risk of TLS or a high risk of TLS and were not scheduled to be treated with rasburicase, were enrolled and then randomized to febuxostat (60 mg/day) or allopurinol (300 or 200 mg/day). All patients started to take the study drug 24 h before chemotherapy. The primary objective was to confirm the non-inferiority of febuxostat to allopurinol based on the area under the curve (AUC) of sUA for a 6-day treatment period., Results: Forty-nine and 51 patients took febuxostat and allopurinol, respectively. sUA decreased over time after initiation of study treatment. The least squares mean difference of the AUC of sUA between the treatment groups was -33.61 mg h/dL, and the 95 % confidence interval was -70.67 to 3.45, demonstrating the non-inferiority of febuxostat to allopurinol. No differences were noted in safety outcomes between the treatment groups., Conclusion: Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy., Trial Registry: http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.

Background: In this study, we investigated the relationship between serum uric acid (SUA) and renal function in a unique patient cohort wherein SUA levels fluctuate during the course of standard care., Methods: Correlation coefficients between SUA and serum creatinine (SCr) and kinetic estimated GFR (KeGFR) were retrospectively investigated in acute myeloid leukemia (AML) patients, and statistically significant and clinically relevant determinants were studied in multiple regression models., Results: One hundred and twenty-six patients were included in the analysis. Baseline SUA was associated with an increased risk for acute kidney injury (AKI; OR 1.27, 95% CI 1.1-1.5, p = 0.003) and laboratory tumor lysis syndrome (OR 1.26, 95% CI 1.1-1.5, p = 0.005). Prophylactic uric acid-lowering therapy and hydration resulted in lower SUA values from baseline in 88.1% of the patients, the lowest values were observed on post-induction day 1 (20.4% reduction). Significant linear correlations were observed between SUA and SCr (r = 0.35, p < 0.001) values with a significant inverse correlation between SUA and KeGFR on day 1 (r = -0.33, p < 0.001) that persisted through day 4. By subgroup analysis, patients with primary AML (r = -0.49, p < 0.001), baseline SUA >5.5 mg/dl (r = -0.41, p = 0.002) and baseline eGFR >60 ml/min/1.73 m2 (r = -0.51, p < 0.001) demonstrated robust relationships between SUA and KeGFR. The relationship was more robust when the groups were combined (primary AML plus baseline SUA >5.5 mg/dl plus baseline eGFR >60 ml/min/1.73 m2, r = -0.52, p < 0.001)., Conclusion: The demonstration of linear relationship between SUA and SCr and inverse relationship between SUA and KeGFR reinforces the emerging translational physiological evidence regarding the role of uric acid in AKI., (© 2016 S. Karger AG, Basel.)

Background: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention., Patients and Methods: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety., Results: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms., Conclusion: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile., Clinical Trial Registration: NCT01724528., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hyperleukocytosis can induce leukostasis, which can lead to vascular obstructions (usually in the lungs and central nervous system), tumor lysis syndrome, and disseminated intravascular coagulation. Although it has not been conclusively shown to improve long-term outcome, leukocytapheresis may be used as part of the management of hyperleukocytosis with or without leukostasis to rapidly reduce the white blood cell (WBC) burden. Since leukocytapheresis only temporarily decreases the WBC count, early initiation of more definite therapy, such as hydroxyurea and/or chemotherapy, is essential. In this article, clinical assessment of the patient's clinical status to determine the need for leukocytapheresis as well as a general guideline for management of the technical aspects and complications of the procedure are discussed., (© 2015 AABB.)

Background: Tumour lysis syndrome is associated with high levels of uric acid, phosphate and potassium along with low levels of calcium and abnormal renal function. Sevelamer, an oral phosphate-binder is used in the treatment of hyperphosphatemia in children and adults on hemodialysis., Case Characteristics: Two children with T-cell acute lymphoblastic leukemia who presented with a high tumour load and developed tumour lysis syndrome., Observation: Both children received Rasburicase and Sevelamer hydrochloride. The serum phosphate reduced to normal levels within 24-48 hrs of initiation of sevelamer hydrochloride., Message: Sevelamer appears to be an effective treatment for hyperphosphatemia associated with tumour lysis syndrome.

The majority of the chemotherapy agents in use today cause various infusion reactions, from mild flushing to life-threatening events. The frequency of the reported hypersensitivity reactions induced by cetuximab varies between 3% and 22%. It is recommended in the literature to stop the infusion and replace cetuximab with panitumumab in case of hypersensitivity reactions observed during the treatment of colon cancer. Tumor lysis syndrome (TLS) may occur in colorectal cancers with heavy tumor load. Tumor lysis syndrome may be life-threatening. In our patient with widespread bone and liver metastases, treatment continued with cetuximab as a combination therapy with irinotecan in spite of the hypersensitivity and TLS led to a complete treatment response. The complete response observed after 3 months through continued therapy in our patient may present an example supporting treatment with cetuximab in spite of severe reactions.

Background: Hyperleucocytosis is associated with higher morbidity and mortality related to possible development of leucostasis, tumour lysis syndrome and/or disseminated intravascular coagulation. There is insufficient evidence of the need for leukocytapheresis during early treatment of hyperleucocytosis, and its efficiency remains controversial, although leucoreduction is a measure that can prevent adverse events and death. The aim of this study was to analyse the safety and effectiveness of therapeutic leukocytapheresis and its influence on early mortality in our case series, adjusted to independent mortality risk factors described in the literature., Materials and Methods: This was a retrospective review (June 2003-June 2012) of procedures carried out for the treatment of hyperleucocytosis at the Haematology and Haemotherapy Service of Miguel Servet University Hospital. The patients' data and technical information were prospectively registered for each leukocytapheresis session., Results: Thirteen patients underwent a total of 27 leukocytapheresis procedures. After an average of two sessions, a statistically significant drop in the initial leucocyte counts was observed (p<0.01), as well as a relevant drop in lactate dehydrogenase levels. The only analytical value statistically related to early mortality in univariate analysis was initial creatinine level greater than 1.2 mg/dL (p=0.012, OR=2.5)., Discussion: Despite the small size and limited homogeneity of our case series, we can conclude that leukocytapheresis is a safe and effective therapeutic measure for leucoreduction in haematological pathologies of any lineage, particularly in patients without acute myeloid leukaemia. Patients with acute myeloid leukaemia had worse outcomes within 6 months of having finished leukocytapheresis sessions, as well as in terms of mean global survival and mean time of mortality. However, global mortality rates were similar in patients with or without acute myeloid leukaemia.

Tumor lysis syndrome (TLS) is an oncologic emergency caused by intense tumor cell destruction resulting in profound electrolyte abnormalities. It is generally recognized as a consequence of cytotoxic therapy in particularly chemotherapy-sensitive tumors such as hematologic cancers. Despite having been primarily recognized in hematologic malignancies, TLS has been reported in solid tumors as well. We present a case of a 72-year-old female who developed TLS after receiving etoposide and carboplatin for a poorly-differentiated carcinoma with areas of small-cell differentiation metastatic to her liver. She had previously undergone a thoracotomy and resection for a poorly differentiated squamous cell cancer of the lung.

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., (© 2013 John Wiley & Sons Ltd.)

What Is Known and Objective: Single-dose rasburicase for the treatment and prevention of hyperuricaemia in adult and paediatric patients with cancer at high risk of tumour lysis syndrome (TLS) has been widely adopted in pharmacy practice as unlabelled use with limited clinical evidence. This meta-analysis study evaluated the efficacy and cost savings of a single-dose rasburicase (SDR) regimen compared with the Food and Drug Administration-approved daily dosing of rasburicase (DDR) for 5 days or the traditional treatment with allopurinol in adult cancer patients with hyperuricaemia or at high risk for TLS., Methods: Prospective and retrospective studies were retrieved from a systemic search of major electronic data sources. Studies included in the meta-analysis were those with SDR for the prophylaxis of high-risk TLS or treatment of hyperuricaemia in adult patients with cancer. The results of response rate and controlling of time-dependent plasma uric acid (UA) reduction were pooled and compared with the results from patients treated with DDR for 5 days or patients treated with allopurinol. A cost analysis was performed to analyse the treatment costs for adults with hyperuricaemia or at high risk for TLS., Results and Discussion: Ten studies (eight retrospective and two prospective) evaluated the SDR response rate and plasma UA level reduction over time. The pooled total number of patients treated with SDR (from 0·05 mg/kg to 0·20 mg/kg) was 269. The pooled response rate of the SDR arm was not significantly different than that of DDR (0·2 mg/kg) arm (88·15% vs. 90·18%, P = 0·542), but significantly stronger than that of allopurinol (300 mg/day orally days 1 to 5) arm (response rate: 88·15% vs. 66%, P < 0·0005). Pooled SDR group efficiently controlled the plasma uric acid (UA) level below 4·5 mg/dL over 24 h, 48 h and 72 h, whereas DDR reduced plasma UA levels to hypouricaemia level (<2 mg/dl). In addition, cost analysis demonstrated that standard-dose SDR (≥6 mg) has non-inferior clinical benefit and significant cost savings compared with the DDR regimen., What Is New and Conclusion: Single-dose rasburicase (SDR) for adult cancer patients with hyperuricaemia or at high risk for TLS demonstrated better response rate and stronger control of uric acid level compared with allopurinol. SDR response rate was not inferior to that of DDR, and the standard-dose SDR generates more cost savings compared with the DDR. It suggests that the single-dose rasburicase is clinically effective and cost efficient for the prophylaxis of high-risk TLS and the treatment of hyperuricaemia in adult patients with cancer. Additional randomized control studies are needed to confirm the findings of this meta-analysis study., (© 2013 John Wiley & Sons Ltd.)

Nilotinib, a second-generation tyrosine kinase inhibitor with 20- to 30-fold greater potency than imatinib, was developed to overcome imatinib intolerance or resistance. Recently, nilotinib has been approved as a first-line treatment for chronic myelogenous leukemia in the US and Japan. Tumor lysis syndrome (TLS) is an extremely rare adverse event that can occur during treatment with nilotinib, with only a few reported cases to date. Herein, we report two patients who developed TLS soon after the start of treatment with nilotinib. While in the first case, which co-presented with underlying mild-to-moderate renal insufficiency due to polycystic kidney disease, the TLS resolved on discontinuation of the drug, the second patient, who had an exceedingly high white blood cell count, presented with disseminated intravascular coagulation and severe liver injury triggered by TLS that developed after the start of nilotinib treatment, and died of multiple organ failure. Therefore, caution is necessary when this drug is used in the first-line setting in patients with renal insufficiency or a high tumor burden.

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., (© 2013 John Wiley & Sons Ltd.)

Background: Rasburicase, used for hyperuricemia of tumor lysis syndrome, retains activity at room temperature (RT) in in vitro studies. Cold-temperature handling is recommended for uric acid measurements in patients receiving rasburicase: collection in prechilled tubes, transportation on ice, and 4°C centrifugation. We performed a prospective study of these requirements., Methods: A total of 65 pairs of blood samples were collected from 34 patients, 12-24 h after receiving rasburicase. The effect of temperature on uric acid concentration was tested on paired samples handled either at RT or when cold: centrifugation (18 sample pairs), collection tube (14 pairs), transportation (24 pairs), and nine pairs were retested after 1 h at RT., Results: No significant temperature effect was seen on the uric acid measurements for any of the cold-handling steps: proportional, absolute biases were -1.4%, -0.06 mg/dL (centrifugation), -1.5%, +0.02 mg/dL (tube temperature), and -2.2%, -0.01 mg/dL (transportation). A 20% negative bias was seen in samples retested after 1 h at RT., Conclusions: Cold handling (prechilled tubes, iced transportation, 4°C centrifugation) was equivalent to RT for immediate measurement. An additional 1 h delay at RT led to a 20% decrease in uric acid. The cold handling measures required by the manufacturer are not necessary for uric acid testing of patients receiving rasburicase treatment, if testing is performed without delay.

Study Objective: To evaluate single fixed dosing versus weight-based dosing strategies for rasburicase to determine the minimum dose required to mitigate hyperuricemia in the treatment or prevention of tumor lysis syndrome., Design: Retrospective medical record review, Setting: Academic medical center, Patients: A total of 373 patients with a diagnosis of a hematologic malignancy or solid tumor and who received at least one dose of rasburicase over a 6-year period between January 1, 2005, and February 18, 2011; 180 patients received single doses of 3 mg (38 patients), 6 mg (99 patients), or 7.5 mg (43 patients), and 193 patients received weight-based dosing., Measurements and Main Results: Tumor lysis syndrome laboratory data were recorded at baseline and monitored up to 72 hours after initial rasburicase administration. Median baseline plasma uric acid levels were 6.85 mg/dl, 8.80 mg/dl, 8.00 mg/dl, and 9.20 mg/dl, respectively, in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups. Treatment success was defined as a normalized plasma uric acid level (< 7.5 mg/dl) within 24 hours after receiving rasburicase. The mean weight-based dose was 0.16 mg/kg. Six rasburicase treatment failures occurred; two were in the 3-mg group, one was in the 6-mg group, and three were in the weight-based dosing group. At 24 hours after rasburicase administration, no statistically significant differences in treatment success were noted among groups (92.9% vs 97.6% vs 100.0% vs 98.0% in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups, respectively, p=0.1238)., Conclusion: The efficacy of all single fixed doses and weight-based dosing strategies evaluated in this study appear to be comparable in normalizing plasma uric acid levels within 24 hours of rasburicase administration. Although use of a 3-mg rasburicase dose may be the most cost-effective treatment strategy in managing hyperuricemia secondary to tumor lysis syndrome, the 6-mg dose resulted in lower sustained uric acid levels after rasburicase administration. Further analysis of patient specific factors contributing to the need for repeat rasburicase administration should be conducted in larger, prospective clinical trials., (© 2013 Pharmacotherapy Publications, Inc.)

Purpose: Recognition of pseudohyperkalemia is essential to prevent medical mismanagement of erroneous hyperkalemia. The purpose of this case is to describe pseudohyperkalemia attributed to malignant leucocytosis in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome. Methods for determination of pseudohyperkalemia are discussed., Summary: A 75-year-old male with progressive chronic lymphoblastic leukemia was hospitalized for medical evaluation and chemotherapy administration. Notable laboratory findings included white blood cell count of 479 × 10(3) cells/µL (4.00 × 10(3) cells/µL-10.80 × 10(3) cells/µL) with 95% lymphocytes (20%-50%) and 5% blasts (zero) present in the differential, serum potassium 9.8 mM/L (3.4 mM/L-5.0 mM/L), uric acid of 11.8 mg/dL (3.5 mg/dL-8.0 mg/dL), serum creatinine 1.47 mg/dL (0.60 mg/dL-1.30 mg/dL), and lactate dehydrogenase of 2529 IU/L (100 IU/L-220 IU/L). The patient was anemic (Hb 7.6 g/dL (14.0 g/dL-18.0 g/dL)) and thrombocytopenic (17 × 10(3) platelets/μL (140 × 10(3) platelets/μL-400 × 10(3) platelets/μL)). There were no electrocardiographic findings indicating systemic hyperkalemia. Repeat analysis of the blood potassium level using a heparinized tube assayed immediately after specimen collection demonstrated a plasma potassium level 4.1 mM/L. Subsequent analysis of specimens using similar methodology demonstrated potassium results within the normal limits despite continued laboratory evidence of pseudohyperkalemia. Based on the patient's conscious and interactive condition, ECG findings, and normal plasma potassium level following immediate analysis, the diagnosis of pseudohyperkalemia was made. Laboratory findings of pseudohyperkalemia persisted throughout the period of leukocytosis., Conclusion: This case describes pseudohyperkalemia attributed to malignant leucocytosis in a patient with chronic lymphoblastic leukemia (CLL). Practitioners should consider pseudohyperkalemia as the underlying cause of elevated potassium levels in patients with malignant leucocytosis who do not have signs or symptoms of systemic hyperkalemia.

A 51-year-old man who underwent umbilical cord blood transplantation for acute lymphoblastic leukemia with a Philadelphia chromosome in April 2006 achieved complete remission. In June 2008, progressive renal dysfunction and melena emerged and the patient was diagnosed with B-cell-type malignant lymphoma. He presented with severe hypo-phosphate- mia(0. 1m g/dL)due to paraneoplastic syndrome, simultaneously. Because the development of tumor lysis syndrome followed by hyper-phophatemia was feared to occur after CHOP chemotherapy, we discontinued the adjustment of serum phosphorus. The serum phosphorus level was elevated to 11.6mg/dL after 3 days and decreased to 3. 8mg/dL after 5 days. We must be careful regarding hyper-phosphatemia and phosphorus adjustment even in patients with severe hypo-phosphatemia that is due to paraneoplastic syndrome.

Aim: Recently, a number of studies have demonstrated the effectiveness of a single reduced dose of rasburicase for the management of tumor lysis syndrome (TLS) in adults. Whether Asian lymphoma patients similarly respond to a single dose of rasburicase is currently unknown. We aim to assess the efficacy of a single dose rasburicase in preventing TLS in Asian lymphoma patients., Methods: This was a single-center case series of adult lymphoma patients at high risk of TLS who received a single fixed dose of rasburicase. Patients had to have their uric acid, serum creatinine, lactate dehydrogenase and electrolytes monitored for at least 24-48 h post-administration., Results: Eleven patients were identified. Majority were Chinese (91%), male (64%) and with a median age of 61 years (range 41-84). All had at least two risk factors for developing TLS. Ten patients received a 6-mg dose and one received 4.5 mg. Prior to rasburicase administration, the mean uric acid level was 835 µmol/L (range 318-1237 µmol/L) and the level 24-h post-administration was 186 µmol/L (range 30-653 µmol/L) (P < 0.001). Eight patients (73%) experienced an improvement of renal function 72-h post-rasburicase. Normalization of serum electrolytes was achieved within 96 h., Conclusion: Among Asian lymphoma patients who manifested at least two risk factors for developing TLS, a single fixed dose of rasburicase at 6 mg is deemed to be effective for rapidly lowering uric acid levels as well as sustaining reduced levels for up to 72 h., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Purpose: Rasburicase is a recombinant urate oxidase enzyme generally reserved for the treatment or prevention of hyperuricemia in patients that are at high risk of developing tumor lysis syndrome (TLS). The primary objective of this study is to evaluate and characterize the outcomes of patients receiving low dose rasburicase for treatment or prophylaxis of hyperuricemia secondary to TLS., Patients/methods: A retrospective chart review between April 1, 2007 and September 31, 2008 was completed. All adult patients who received a dose of 0.05mg/kg with either a leukemia or lymphoma diagnosis in addition to at least two TLS risk factors: WBC ≥ 50 × 109/L, LDH 2 × ULN, uric acid ≥ 8 mg/dl, SCr ≥ 1.5 mg/dl were included. Forty-eight patients received rasburicase for prophylaxis (n = 18) or treatment (n = 30) of TLS., Results: Forty patients achieved and maintained a uric acid less than 8 mg/dL, 24 h after receipt of a single dose of rasburicase without the requirement for renal replacement therapy. A statistically significant decrease in UA was achieved in all patients when compared to baseline (p < 0.001). Cost analysis revealed a $ 1.96 million (96%) direct cost savings for the 48 patients in this study when compared to the cost of manufacturer's dosing recommendation., Conclusions: Low dose rasburicase was efficacious and cost effective for both prophylaxis and treatment of TLS. Administration of a single dose of 0.05mg/kg of rasburicase was sufficient in correcting uric acid levels for most patients.

The tumor lysis syndrome (TLS) is a life-threatening complication caused by the massive release of nucleic acids, potassium and phosphate into the blood. This complication is the result of tumor cell lysis, which may occur due to treatment of drug sensitive and is characterized by rapid capacity of proliferation, that is often hematological origin. Moreover, the TLS can be observed before starting the treatment due to spontaneous tumor cell death, and frequently worsens when chemotherapy is initiated. TLS has high mortality, so that its prevention continues to be the most important therapeutic measure. In the intensive care unit (ICU), physicians should be aware of the clinical characteristics of TLS, which results in severe electrolyte metabolism disorders, especially hyperkalemia, hyperphosphatemia and hypocalcemia, and acute kidney injury which is a major cause of ICU mortality. An adequate strategy for the management of the TLS, combining hydration, urate oxidase, and an early admission to ICU can control this complication in most patients. The aim of this review is to provide diagnostic tools that allow to the ICU physician to recognize the population at high risk for developing the TLS, and outline a proper strategy for treating and preventing this serious complication., (© 2010 Elsevier Espa˜na, S.L. y SEMICYUC. All rights reserved.)

Background: Merkel cell carcinoma (MCC) is a rare, highly malignant cancer of the skin primarily affecting the elderly, with a tendency for local recurrence and regional lymph node metastasis. It is very unusual for this kind of tumor to induce clinically apparent tumor lysis syndrome (TLS) which is a consequence of spontaneous cytolysis or massive tumor cell lysis, beginning a few hours after the initiation of treatment., Case Report: We report here on a patient with metastatic MCC, who developed TLS following combination chemotherapy with carboplatin and etoposide., Conclusion: The evolving acute kidney injury (AKI) provoked a pathologic sequence of reduced renal clearance leading to protracted clearance of carboplatin and subsequent fatal pancytopenia. When AKI occurs in close association with the administration of carboplatin, the institution of rescue hemodialysis is recommended to decrease plasma carboplatin levels and avoid this lethal complication., (Copyright © 2011 S. Karger AG, Basel.)

Tumor lysis syndrome has been observed in patients with bulky, treatment-sensitive tumors, in particular hematological malignancies, especially after medical treatment (chemotherapy, corticosteroids, radiation, hormonal agents, and biological response modifiers). Tumor lysis syndrome has been observed also in solid malignancies and it very rarely occurs spontaneously. Tumor lysis syndrome-associated metabolic abnormalities include hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia and uremia. Severe hypoglycemia is another rare metabolic disorder, uncommonly associated with solid malignancies. The case described here is peculiar for the abrupt onset of these two rare conditions in a patient with a metastatic germ cell tumor.

Background: Rasburicase is indicated for the initial management of plasma uric acid levels in adults receiving anticancer therapy who are at risk for acute tumor lysis syndrome (TLS) and subsequent hyperuricemia. The labeled dose is 0.2 mg/kg/day administered intravenously over 30 minutes for up to 5 days. Our institutional adult guidelines recommend rasburicase 6 mg for uric acid levels >8 mg/dL in most adults with TLS, or 4-8 mg/dL in high-risk patients. Repeat dosing is indicated for uric acid levels >4 mg/dL determined ≥12 hours following the initial dose., Objective: To determine the efficacy of a single dose of rasburicase 6 mg per institutional adult TLS guidelines to decrease uric acid levels to <4 mg/dL by day 3, as well as to determine the effect on serum creatinine and phosphorus concentrations. The secondary objectives were to evaluate the appropriateness of our institutional guidelines and identify TLS risk factors., Methods: The study was approved by the University of Maryland Medical Center Institutional Review Board. A retrospective review of all adults between July 2008 and February 2009 who received at least one 6-mg dose of rasburicase, with redosing, if indicated, before day 3, was conducted. Subsequent TLS monitoring over 7 days after initial dosing was recorded. Patients were excluded if dosing did not adhere to institutional guidelines., Results: We observed a decline in median uric acid levels from 9.2 mg/dL (interquartile range 8.1-10.4) on day 1 to between 1.8 (1.0-3.8) on day 3 and 3.8 mg/dL (2.1-4.4) on day 7 (p < 0.0001) with 2 patients requiring repeat dosing before day 3 (n = 34). The majority of the population was hyperuricemic (>8 mg/dL; 76%) or at high risk for TLS (85%)., Conclusions: A 6-mg dose of rasburicase effectively decreased uric acid to <4 mg/dL by day 3, rarely requiring repeat dosing, in a high-risk population.

Purpose: Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid., Patients and Methods: Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.20 mg/kg/d intravenously days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/d days 1 to 3 followed by oral allopurinol 300 mg/d days 3 to 5), or allopurinol (300 mg/d orally days 1 to 5). Primary efficacy variable was plasma uric acid response rate defined as percentage of patients achieving or maintaining plasma uric acid ≤ 7.5 mg/dL during days 3 to 7., Results: Ninety-two patients received rasburicase, 92 rasburicase plus allopurinol, and 91 allopurinol. Plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol. It was significantly greater for rasburicase than for allopurinol (P = .001) in the overall study population, in patients at high risk for TLS (89% v 68%; P = .012), and in those with baseline hyperuricemia (90% v 53%; P = .015). Time to plasma uric acid control in hyperuricemic patients was 4 hours for rasburicase, 4 hours for rasburicase plus allopurinol, and 27 hours for allopurinol., Conclusion: In adults with hyperuricemia or at high risk for TLS, rasburicase provided control of plasma uric acid more rapidly than allopurinol. Rasburicase was well tolerated as a single agent and in sequential combination with allopurinol.

Spontaneous tumour lysis syndrome (STLS) inducing acute uric acid nephropathy, a rare and neglected disease, presents more insidiously than conventional post-treatment tumour lysis syndrome. Although STLS is a serious and potentially fatal complication in patients with neoplastic disorders, few investigations have addressed the relevance of clinical and laboratory features in assessing prognosis. A retrospective study was conducted, reviewing the records of all patients who developed acute renal failure (ARF) at Chang Gung memorial hospital between 1 July 1999 and 30 June 2003. STLS-induced acute uric acid nephropathy was identified in 12 of 1072 ARF patients (1.1%) during the study period. All patients had advanced stage tumours with large tumour burden, and 66.7% of cases had abdominal organ involvement. All 12 hyperuricemic patients became oliguric despite conservative therapy, and remained hyperuricemic (21.6 +/- 5.2 mg/dl) before dialysis therapy. Diuresis developed in eight patients (66.7%), with associated resolution of hyperuricemia, azotemia and metabolic derangements following dialysis initiation. Overall hospital mortality was 58.3%. Death in most patients was related to hyponatremia and hypoalbuminemia on admission. The serum sodium was found to have the best Youden index (0.86) and highest overall prediction accuracy (93%). Moreover, serum sodium and serum albumin for individual patients were significantly and positively correlated (r = 0.617, p = 0.032). This investigation confirms a grave prognosis for cancer patients with STLS inducing acute uric acid nephropathy. Hyponatremia and hypoalbuminemia on the first day of admission indicate poor prognosis in such patients.

Objective: To examine the role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the efficacy of continuous hemodiafiltration in the treatment of TLS., Design and Setting: Retrospective observational study in a general intensive care unit of a university hospital., Patients: Four patients with hematological disorder developing TLS after the treatment of anti-tumor chemotherapy., Interventions: Continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) was performed at the onset of TLS. Blood samples were collected daily after ICU admission, and clinical parameters and blood levels of cytokines were evaluated., Measurements and Results: All four patients underwent induction anti-tumor chemotherapy, during which they developed hyperuricemia, hyperkalemia, and acute renal failure. Two of them also developed multiple organ failure. Serum levels of tumor necrosis factor (TNF) -alpha, interleukin-6 (IL-6), and IL-10 prior to the initiation of PMMA-CHDF were 102+/-85 pg/mL, 1097+/-546 pg/mL, and 98+/-83 pg/mL, respectively (mean +/- SD). After three days of PMMA-CHDF treatment, corresponding blood levels were 37+/-55 pg/mL, 326+/-511pg/mL, and 9+/-8 pg/mL, respectively. Thus, all cytokine levels were significantly decreased by three days of PMMA-CHDF treatment (p<0.05, paired t-test). Following three days of PMMA-CHDF treatment, blood urea nitrogen (BUN) and serum creatinine (Cre.) were significantly decreased (pre/post BUN 42.3+/-15.4/16.5+/-8.4 mg/dL, p<0.05, pre/post Cre. 2.7+/-1.2/1.2+/-0.6 mg/dL, mean +/- SD, p<0.05). Furthermore, the clinical condition of each patient was improved after the treatment of PMMA-CHDF, and all of four patients were survived., Conclusion: Hypercytokinemia plays a pivotal role in the pathophysiology of TLS and PMMA-CHDF may be an effective therapeutic modality for TLS patients not only as renal replacement therapy but also as a cytokine modulator.

Recently, the ASCO guideline has added TLS. Prevention and recognition of the disease and state are important. Molecular targeting drugs, small molecule tyrosine kinase inhibitors and monoclonal antibodies induced rapid regression of the tumors and carry a risk of TLS. The recognition of the disease which may have a high risk of TLS and laboratory TLS is important.

We report here a case of esophageal cancer patient who developed tumor lysis syndrome after chemotherapy. A 57- year-old man received esophagectomy for advanced esophageal cancer. CT study revealed multiple lymphnode metastases, multiple bone metastases and multiple lung metastases after 15 months from the operation. So, chemotherapy was performed for the patient. Eleven days following the administration of docetaxel: 30 mg/m2 and nedaplatin: 30 mg/m2, the patient developed TLS (serum creatinine: 8.57 mg/dL, uric acid: 11.0 mg/dL, serum potassium: 6.3 mEq/L, serum phosphorus: 7.18 mg/dL). The patient responded well to an appropriate treatment with a combination of vigorous intravenous hydration, carperitide, allpurinol and potassium citrate sodium citrate. This case report describes the first patient to develop TLS following chemotherapy for esophageal cancer.