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Tumor lysis syndrome (TLS) is a commonly observed oncological emergency that requires prompt diagnosis and treatment. Rasburicase is a recombinant urate oxidase endorsed in TLS for the treatment of hyperuricemia. The effect of single-dose 7.5 mg rasburicase at longer follow-ups was not widely investigated.Eighty-two patients included in the study with clinical TLS and laboratory TLS. The primary endpoint was the normalization of uric acid (6mg/dL) within 24 hours of rasburicase administration, which was described as treatment success. The secondary endpoint was defined as having sustained response at the first week. The third endpoint was defined as the reaching the baseline renal function before TLS.We found that the use of a 7.5 mg dose of rasburicase controlled uric acid in 74 of 82 (90,2%) patients at the 24th hour. In the first week, uric acid remained at normal levels in 69 of 82 (84,1%) patients. At 24 hours, the TLS risk group was the only predictor for failing uric acid normalization; at the end of the first week, no predictive factor was identified for failing uric acid normalization.Rasburicase at 7.5 mg dose is an important agent for controlling laboratory and clinical TLS at 24 hours and extending its effect to the first week.

Uric acid drives acute kidney injury in tumor lysis syndrome (TLS). This study investigated the relationship between uric acid and changes in estimated glomerular filtration rate (eGFR) in adults at risk for TLS. Linear regression was used to evaluate the relationship between uric acid area under the curve (AUC) and percent change in eGFR from baseline at hospital dismissal, 1 and 3 months. In 210 included participants, each 100 mg*hour/dL increase in 24 h AUC was associated with an average decline in eGFR at hospital dismissal of 9% (95%CI 3, 15) in univariate analysis. Each 100 mg*hour/dL increase in 24 h AUC was independently associated with an average decline in eGFR of 8% (95%CI 2, 13) at 1 month after dismissal. Additional research is needed to confirm these findings and determine whether treatments that reduce overall uric acid exposure improve kidney outcomes. Preserving kidney health could favorably impact cancer treatment eligibility, tolerability, and outcomes.

BACKGROUND Rasburicase (recombinant urate oxidase) has been proven to be an effective therapy for prevention of tumour lysis syndrome (TLS). The recommended daily dosing regimen of rasburicase is 0.2 mg/kg/day for 5 days which is expensive and unaffordable to many patients in the developing countries. The purpose of the present study was to evaluate the effect of single 1.5 mg dose rasburicase in the management of tumour lysis syndrome. METHODS This is a follow-up study done at our institute. Fifty (50) patients with tumour lysis syndrome who received rasburicase from August 2015 to January 2020 were enrolled in this study RESULTS Single dose of rasburicase is effective in decreasing serum uric acid level in significant number (N = 41) of patients. Percentage of patients having uric acid less than 7 mg after single dose of rasburicase in 48 hours - 82.9 % (N = 34) while 17 % (N = 7) were found to have uric acid levels of more than 7 mg/dl. The percentage of patients with uric acid levels more than 7 mg/dl reduced from 36.5 % after 24 hours to 17 % after 48 hours. This indicates that the uric acid levels show a declining trend even after 24 hours without giving an additional dose of rasburicase. There was no relationship between uric acid levels at 24 hours and percentage change in creatinine level from baseline to 24 hours (correlation coefficient (r) = -0.047, P = 0.770. Patients who required additional dose (N = 9) had high base line value of uric acid and their high value was maintained over the follow up period of three days. Patients with pre exiting kidney disease and high level of baseline uric acid also needed dialysis (N = 3). CONCLUSIONS In majority of patients, a single 1.5 mg dose of rasburicase is an effective way to reduce raised uric acid in appropriate circumstances. KEYWORDS Single Dose, Recombinant Urate Oxidase, Uric Acid, Leukemia, Tumour Lysis Syndrome, Rasburicase

Tumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS.We planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid7.5 mg/dL were included. The primary endpoint was uric acid normalization (7.5 mg/dL) within 24 hours of rasburicase administration.Fifty-five patients were recruited for this study. Pediatric patients (18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose.Single-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.

Tumor lysis syndrome is an oncological emergency, which can ultimately lead to death if not recognized early and treated accordingly. The institution of adequate prophylactic measures can decrease its incidence and severity; but very rarely, a highly aggressive neoplasm such as acute lymphoblastic leukemia or Burkitt’s lymphoma can present with spontaneous tumor lysis syndrome (sTLS). We present the case of a 58-year-old male with newly diagnosed plasmablastic lymphoma with a retroperitoneal bulky mass invading the bladder, who presented with severe sTLS and was admitted to an intensive care unit due to acute renal failure and hyperkalemia requiring emergent renal replacement therapy. With urgent chemotherapy, several hemodialysis sessions and rasburicase, all the metabolic derangements were corrected and the patient fully recovered a normal renal function. This report highlights the importance of early recognition of sTLS in any patient presenting with severe and de novo multiple metabolic derangements involving uric acid, phosphorus, calcium and creatinine, even in patients with tumors not usually presenting with this complication.

Background The recommended dose of rasburicase is quite expensive, thus limiting its use. Whether a lower dose of rasburicase would be equally effective for critically ill children, who often have more complicated situations and a higher risk of hospital death, is still unknown. Objective To explore the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies who are at high risk of tumour lysis syndrome. Setting A single-centre retrospective cohort study. Method Children with haematological malignancies who had a history of rasburicase exposure during an intensive care unit stay were enrolled. Patients were divided into two groups according to the initial dosage of rasburicase: the standard-dose group (> 0.1 mg/kg/day) and the low-dose group (≤ 0.1 mg/kg/day). The adverse events and short-term prognosis of the two groups were compared. Results Thirty-seven children were selected, 22 in the standard-dose group and 15 in the low-dose group. The most common tumour type was Burkitt’s lymphoma (81%), followed by acute lymphoblastic leukaemia (11%). All patients were at high risk of tumour lysis syndrome, and 73% of them had 3 or more tumour lysis syndrome risk factors. The uric acid levels of 90% of patients with hyperuricaemia returned to the normal range within 12 h (100% in the standard-dose group and 75% in the low-dose group, P = 0.083). Eighty-four percent of patients presented serious complications, including tumour lysis syndrome (73%), acute kidney injury (59%), renal replacement treatment (24%), respiratory failure (24%), disseminated intravascular coagulation (16%) and heart failure (11%). There was no significant difference in the incidence of serious complications between the two groups. The overall 7-day and 28-day survival rates after intensive care unit admission were 86% and 84%, respectively. The average length of stay in the intensive care unit was 9.92 ± 5.13 days. Neither the short-term mortality nor the length of stay in the intensive care unit were significantly different between the two groups. Conclusion Low-dose rasburicase is effective and may be an acceptable choice for critically ill children with haematological malignancies.

Background Multiorgan failure is a consequence of severe ischemia-reperfusion injury after traumatic hemorrhagic shock (HS), a major cause of mortality in trauma patients. Circulating uric acid (UA), released from cell lysis, is known to activate proinflammatory and proapoptotic pathways and has been associated with poor clinical outcomes among critically ill patients. Our group has recently shown a mediator role for UA in kidney and lung injury, but its role in liver and enteric damage after HS remains undefined. Therefore, the objective of this study was to evaluate the role of UA on liver and enteric injury after resuscitated HS. Methods A murine model of resuscitated HS was treated during resuscitation with a recombinant uricase, a urate oxidase enzyme (rasburicase; Sanofi-Aventis, Canada Inc, Laval, Canada), to metabolize and reduce circulating UA. Biochemical analyses (liver enzymes, liver apoptotic, and inflammatory markers) were performed at 24 hours and 72 hours after HS. Physiological testing for enteric permeability and gut bacterial product translocation measurement (plasma endotoxin) were performed 72 hours after HS. In vitro, HT-29 cells were exposed to UA, and the expression of intercellular adhesion proteins (ZO-1, E-cadherin) was measured to evaluate the influence of UA on enteric permeability. Results The addition of uricase to resuscitation significantly reduced circulating and liver UA levels after HS. It also prevented HS-induced hepatolysis and liver apoptotic/inflammatory mediators at 24 hours and 72 hours. Hemorrhagic shock-induced enteric hyperpermeability and endotoxemia were prevented with uricase. Conclusions After resuscitated HS, UA is an important mediator in liver and enteric injury. Uric acid represents a therapeutic target to minimize organ damage in polytrauma patients sustaining HS.

Spontaneous tumor lysis syndrome is an uncommon oncologic emergency. It occurs when a massive number of malignant cells release their contents to the blood stream without previous cancer treatment. TLS carries a mortality rate exceeding 15%. Because of the high mortality rate, the key to the management of TLS continues to be early recognition of high-risk patients and using prophylactic measures to prevent its occurrence. However, it remains difficult to completely eradicate TLS, as a small proportion of patients with aggressive tumors develop spontaneous TLS prior to receiving any therapy. We present a case of 58-year-old male with recently diagnosed multiple myeloma. He was found to have hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, elevated LDH levels, and acute renal failure, fulfilling the criteria of clinical TLS. He was treated with rasburicase, continuous renal replacement therapy, and dexamethasone.

ObjectivesAcquired methemoglobinemia (MetHb) is an uncommon presentation of cyanosis in the pediatric emergency department (ED), making its diagnosis and management a clinical challenge. Through this case series we hope to improve clinician ability to recognize the potential for MetHb in pediatric ED patients and to avoid overlooking this important cause of cyanosis.MethodsThis was a case series using a health records review, investigating patients diagnosed with MetHb at our pediatric ED during 2007–2018. We included only cases with methemoglobin saturation ≥5%.ResultsTen patients were diagnosed with MetHb in our pediatric ED during the study period. Five had an underlying hematologic disease who received a pharmacologic trigger known to induce MetHb as well (four dapsone, one rasburicase). The other five patients were previously healthy, who presented with a clinical picture of hemolytic anemia, all of whom were diagnosed with previously unknown glucose-6-phosphate dehydrogenase (G6PD) deficiency. Two of the patients received methylene blue, and five patients needed packed red blood cells. All of the patients survived the acute MetHb episode.ConclusionAcquired MetHb in the pediatric ED is a rare but important cause of cyanosis. Diagnosis and management of acute, acquired MetHb in the ED requires a high level of suspicion, and a background knowledge of the common precipitants and underlying conditions associated with this condition. We hope this case series will help ED physicians to consider MetHb in pediatric patients presenting with cyanosis and persistent hypoxia. Exposure to known precipitants (e.g., medications and foods), particularly in the setting of active treatment for malignancy or with symptoms of hemolytic anemia should further increase suspicion.

Background: Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and serious clinical consequences such as acute renal injury, cardiac arrhythmia, hypotension, and death. Rapidly expanding knowledge of cancer immune evasion mechanisms and host-tumor interactions has significantly changed our therapeutic strategies in hemato-oncology what resulted in the expanding spectrum of neoplasms with a risk of TLS. Summary: Since clinical TLS is a life-threatening condition, identifying patients with risk factors for TLS development and implementation of adequate preventive measures remains the most critical component of its medical management. In general, these consist of vigilant laboratory and clinical monitoring, vigorous IV hydration, urate-lowering therapy, avoidance of exogenous potassium, use of phosphate binders, and – in high-risk cases – considering cytoreduction before the start of the aggressive agent or a gradual escalation of its dose. Key Messages: In patients with a high risk of TLS, cytotoxic chemotherapy should be given in the facility with ready access to dialysis and a treatment plan discussed with the nephrology team. In the case of hyperkalemia, severe hyperphosphatemia or acidosis, and fluid overload unresponsive to diuretic therapy, the early renal replacement therapy (RRT) should be considered. One must remember that in TLS, the threshold for RRT initiation may be lower than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted.

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.

Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. It is characterized by massive tumor cell death leading to metabolic derangements and multiple organ failure. It is a rare complication of hepatocellular carcinoma (HCC) with only a few cases have been reported in the literature to date. We collected and summarized published case reports of tumor lysis syndrome in patients with HCC. We also reported one additional case who developed TLS after sorafenib therapy and wrote a clinical vignette. A comprehensive and current search for relevant articles was conducted in Medline and EMbase through May 2018. A systematic review was performed following the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 28 cases of TLS associated with HCC were enrolled in our review. The median age of included cases was 55.5 years with a male to female ratio of 25:3. The two most common attributed factors of TLS were transcatheter arterial chemoembolization (TACE) (12 cases, 42.9 %) and sorafenib (nine cases, 32.1%). Among enrolled cases, the diameter of the largest tumor was 12 cm. Regarding Barcelona Clinic Liver Cancer (BCLC) staging, seven cases were at least stage A (22.6%), 11 cases were at least stage B (35.5%), and 10 cases were at least stage C (32.3%). The median time of onset of TLS was three days. As for uric acid-lowering agents, nine cases (32.1%) used allopurinol and four cases (14.3%) used rasburicase. Ten cases (35.7%) did not specify the medication prescribed. The overall mortality rate of this cohort was 67.9%. Compared with patients developing TLS following TACE, patients who had TLS following sorafenib therapy had a later onset of TLS (two days versus seven days, p < 0.001) and a more advanced stage of HCC (p = 0.002). There was a trend toward increased mortality of patients in the sorafenib group in comparison with those in the TACE group (77.8% versus 41.7%, p = 0.18). The results of this current review suggest that TLS rarely occurs in HCC but carries significantly higher mortality compared to TLS occurring in hematologic malignancies. It may occur shortly after TACE or with a delayed onset following sorafenib therapy. Considering the kaleidoscope of novel therapies and diverse pathogenesis of HCC, it is crucial for clinicians to recognize the clinicolaboratory derangements suggestive of TLS and initiate appropriate management. The present review highlights the need for clinicians to consider TLS within differentials when caring for patients with HCC.

Background Tumor lysis syndrome (TLS) is a known oncologic emergency characterized by severe metabolic derangements. TLS has been well documented in patients with hematologic malignancies, but rarely with metastatic melanoma. The objective of this study was to investigate the clinical characteristics and outcomes of TLS with metastatic melanoma. Methods Retrospective literature review and analysis. Results Eighteen cases of TLS were identified with metastatic melanoma from published literature. The median age of patients was 63 years (36-79 years). All patients have stage IV disease. Seven cases (39%) of TLS were associated with multiple treatment regimes, including nivolumab (22%), ipilimumab (16%), and dacarbazine (22%). The time from treatment to diagnosis was 3.5 days (8 hours-21 days) in treatment-related TLS. Three cases (17%) were due to spontaneous TLS. The majority of cases have a high tumor burden (77.5%) and liver metastasis (83%). Seven cases were treated with rasburicase (39%). The mortality rate was 100% for the patients with spontaneous TLS and 73% for patients with treatment-related TLS. Three cases utilized traditional chemotherapy and the six most recent cases of treatment-associated TLS utilized immunotherapy and targeted therapy. Conclusion TLS in metastatic melanoma, due to either spontaneous or treatment-related causes, is associated with a very high mortality rate. This study highlights the importance of awareness, early intervention, and risk assessment of this underdiagnosed emergency.

Certain clinical indications and treatments such as the use of rasburicase in cancer therapy and 8-aminoquinolines for Plasmodium vivax malaria treatment would benefit from a point-of-care test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three studies were conducted to evaluate the performance of one such test: the STANDARD™ G6PD Test (SD BIOSENSOR, South Korea). First, biological interference on the test performance was evaluated in specimens with common blood disorders, including high white blood cell (WBC) counts. Second, the test precision on fingerstick specimens was evaluated against five individuals of each, deficient, intermediate, and normal G6PD activity status. Third, clinical performance of the test was evaluated at three point-of-care settings in the United States. The test performed equivalently to the reference assay in specimens with common blood disorders. High WBC count blood samples resulted in overestimation of G6PD activity in both the reference assay and the STANDARD G6PD Test. The STANDARD G6PD Test showed good precision on multiple fingerstick specimens from the same individual. The same G6PD threshold values (U/g Hb) were applied for a semiquantitative interpretation for fingerstick- and venous-derived results. The sensitivity/specificity values (95% confidence intervals) for the test for G6PD deficiency were 100 (92.3–100.0)/97 (95.2–98.2) and 100 (95.7–100.0)/97.4 (95.7–98.5) for venous and capillary specimens, respectively. The same values for females with intermediate (> 30% to ≤ 70%) G6PD activity were 94.1 (71.3–99.9)/88.2 (83.9–91.7) and 82.4 (56.6–96.2)/87.6(83.3–91.2) for venous and capillary specimens, respectively. The STANDARD G6PD Test enables point-of-care testing for G6PD deficiency.

Aims We investigated sex and racial inequalities in clinical trials testing serum uric acid (SUA) lowering drugs and analyzed the temporal trends of participation among the pre-specified demographic groups. Data were collected from publications of clinical trials testing SUA-lowering drugs. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled in clinical studies. Data synthesis The mean percentage enrollment of women in clinical trials significantly decreased over the time (r = −0.43, P-value = 0.02). Moreover, there was a statistically significant difference in mean percentage enrollment of women among trials testing different SUA-lowering drugs, with the highest representation in rasburicase (71.1%) and the lowest representation of women in dotinurad (0.8%). Over the time, also the mean percentage enrollment of racial minorities decreased, passing from 8.7% to 2.2% in a 10-year period. Women were proportionally underrepresented compared with their share of the population with asymptomatic hyperuricemia, overall (participation-to-prevalence ratio (PPR) = 0.34), in trials testing xanthine oxiase inhibitors (PPR = 0.38) and uricosurics (PPR = 0.29), and in trials with febuxostat, allopurinol, pegloticase, halofenate/arhalofenate, verinurad, lesinurad and dotinurad. Women were proportionally underreppresented also compared with their share of the population with gout, overall (PPR = 0.69) and in trials testing XOIs (PPR = 0.69), uricosurics (PPR = 0.68), and all SUA-lowering drugs excepted for rasburicase, pegloticase and topiroxostat. Conclusions Our analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.

We hypothesized acute moderate and drastic reductions in uric acid concentration exert different effects on arterial function in healthy normotensive and hypertensive adults. Thirty‐six adults (aged 58 [55;63] years) with or without primary hypertension participated in a three‐way, randomized, double‐blind, crossover study in which [placebo] and [febuxostat] and [febuxostat and rasburicase] were administered. Febuxostat and rasburicase reduce the uric acid concentration by xanthine oxidoreductase inhibition and uric acid degradation into allantoin, respectively. Endothelial function was assessed in response to acetylcholine, sodium nitroprusside, heating (with and without nitric oxide synthase inhibition) using a laser Doppler imager. Arterial stiffness was determined by applanation tonometry, together with blood pressure, renin–angiotensin system activity, oxidative stress, and inflammation. Uric acid concentration was 5.1 [4.1;5.9], 1.9 [1.2;2.2] and 0.2 [0.2;0.3] mg/dL with [placebo], [febuxostat] and [febuxostat–rasburicase] treatments, respectively (p, Acute moderate hypouricemia encompasses minor improvements in endothelial function, blood pressure, and arterial stiffness.

Introduction Tumor lysis syndrome is an oncologic emergency characterized by hyperuricemia. Previous studies have demonstrated that a fixed-dose strategy of rasburicase is as effective as the FDA approved weight-based dose. Albany Medical Center employs rasburicase 1.5 mg in patients with a uric acid (UA) between 8 and 12 mg/dL and 3 mg for UA above12 mg/dL.We aimed to evaluate the UA lowering effectiveness and provider adherence to the institutional protocol, as well as the cost-efficiency of this dosing strategy. Methods This is a single center, retrospective, cohort study. The electronic medical record was used to identify patients receiving rasburicase and to collect baseline demographic and laboratory data. The fixed-dose strategies of rasburicase 1.5 mg and 3 mg were compared in their degree of UA reduction and clinical outcomes. Cost-savings of fixed-dosing was compared to the FDA-approved weight-based dose. Results Mean UA reduction in the 1.5 mg group (n = 49) from baseline to 24 hours was 2.88 ± 0.88 mg/dL (p Conclusion Low fixed-dose rasburicase was an effective treatment, with a dose of 1.5 mg being sufficient to reach a goal UA of less than 8 mg/dL for serum UA levels below 12 mg/dL, while a 3 mg dose is appropriate for levels above 12 mg/dL. Cost analysis indicates this strategy is more cost-efficient than the FDA-approved weight-based dose.

Introduction Tumor lysis syndrome is a rare and potentially fatal complication of oncological treatment. It is characterized by biochemical changes associated with the rapid lysis of malignant cells, usually after chemotherapy. Tumor lysis syndrome is typically noted in patients with hematological malignancies, and it rarely occurs in patients with solid tumors. Case presentation We report a case of tumor lysis syndrome after cabazitaxel administration for metastatic castration-resistant prostate cancer. To our knowledge, tumor lysis syndrome after cabazitaxel therapy has not been reported previously. The patient was a 77-year-old man who developed clinical tumor lysis syndrome after a single dose of cabazitaxel for metastatic castration-resistant prostate cancer. He was treated with hydration and the recombinant uricolytic agent rasburicase, and his condition improved. Conclusion It is extremely important to assess the risk factors for tumor lysis syndrome and to perform active prevention procedures in order to avoid fatal outcomes. It may be beneficial to use rasburicase in patients with established tumor lysis syndrome.

Purpose Due to an increased use of rasburicase, the study’s purpose was to evaluate both the management of tumor lysis syndrome and the utilization of rasburicase in the hospital system. Additionally, the efficacy of flat dose rasburicase in lowering uric acid levels was evaluated. Based on the study’s findings, the investigators will evaluate the usefulness of implementing a tumor lysis syndrome order set. Methods This study evaluated patients from January 2013 through December 2016 for the rasburicase dose and the tumor lysis syndrome therapy administered. Results Overall, 251 patients were included: prophylactic rasburicase group (n = 125) vs. treatment rasburicase group (n = 126) and of rasburicase 3 mg (R3) group (n = 168) vs. 6 mg (R6) group (n = 83). The prophylactic rasburicase vs. treatment rasburicase group had a significantly lower rate of receiving a xanthine oxidase inhibitor (48.0% vs. 64.3%, p = 0.009), a phosphate binder (6.4% vs. 17.5%, p = 0.007) and an additional dose of rasburicase (20.8% vs. 41.3%, p = 0.001). Intravenous hydration was neither significantly different between the rasburicase groups (p = 0.399) nor between the two rasburicase dosing groups (p = 0.874). Between the rasburicase dosing groups, there was no significant difference in the rate of receiving a xanthine oxidase inhibitor (p = 0.521) or a phosphate binder (p = 0.390). R6 patients had a significantly greater reduction in uric acid change compared to R3 patients (median = −7.9 (−10.1, −5.5) vs. −4.3 (−6.0, −2.7), p Conclusion The study’s findings justified the need to implement a tumor lysis syndrome order set. In the study population, utilizing a flat dosing method was effective for hyperuricemia.

Tumour lysis syndrome (TLS) is a life-threatening emergency characterised by a massive cytolysis with the release of intracellular electrolytes, nucleic acids, and metabolites into the circulation. TLS comprises laboratory derangements (hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia) responsible for acute kidney injury. In patients with hematologic malignancies after cytotoxic therapy or spontaneously and also in advanced solid tumours. Assessment of disease specific risk level for TLS in patients receiving anti-tumoural therapy is essential for early diagnosis. Prophylaxis is the mainstay of management of TLS. It is important to routinely initiate a risk-adapted prophylactic strategy to correct metabolic alterations and preserve renal function. High and intermediate risk patients and patients with established TLS should be managed with multidisciplinary medical care in a hospital unit to receive monitoring and medical care. Renal replacement therapy should be considered in patients with refractory TLS.

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective. Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin's lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively. Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative. Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.

Background Multiple organ failure can develop after hemorrhagic shock (HS). Uric acid (UA) is released from dying cells and can be proinflammatory. We hypothesized that UA could be an alternative mediator of organ apoptosis and inflammation after HS. Methods Ventilated male Wistar rats were used for the HS model. Two durations of shock (5 minutes vs. 60 minutes) were compared, and shams were instrumented only; animals were resuscitated and observed for 24 hours/72 hours. Caspases-(8/3), myeloperoxidase (MPO), TNF-α were measured in lungs and kidneys. Plasma UA and cytokine (IL-1β, IL-18, TNF-α) were measured. A second set of animals were randomized to vehicle versus Rasburicase intraperitoneal intervention (to degrade UA) during resuscitation. Another group received exogenous UA intraperitoneally without HS. Measures mentioned above, in addition to organs UA, were performed at 24 hours. In vitro, caspases-(8/3) activity was tested in epithelial cells exposed to UA. Results Hemorrhagic shock increased organ (kidney and lung) TNF-α, MPO, and caspases activity in various patterns while caspase-8 remained elevated over time. Hemorrhagic shock led to increased plasma UA at 2 hours, which remained high until 72 hours; TNF-α and IL-18 were elevated at 24 hours. The exogenous UA administration in sham animals reproduced the activation of caspase-8 and MPO in organs, and TNF-α in the lung. The increased plasma and organ UA levels, plasma and lung TNF-α, as well as organ caspase-(8/3) and MPO, observed at 24 hours after HS, were prevented by the administration of Rasburicase during resuscitation. In vitro, soluble UA induced caspases-(3/8) activity in epithelial cells. Conclusion Uric acid is persistently high after HS and leads to the activation of caspases-8 and organ inflammation; these can be prevented by an intervention to degrade UA. Therefore, UA is an important biomarker and mediator that could be considered a therapeutic target during HS resuscitation in human.

Tumor lysis syndrome is a constellation of metabolic derangements seen when tumor cells die and release their intracellular contents into the systemic circulation. Hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia may lead to severe organ dysfunction and even death. Tumor lysis syndrome is classically considered a complication of successful cancer treatment, but it can also occur in untreated malignancies characterized by rapid proliferation. In this review, we cover the types of cancers and chemo- and immunotherapies associated with tumor lysis syndrome, the mechanisms by which severe metabolic derangements can develop, and the available treatments.

BACKGROUND: Rasburicase is a recommended treatment of tumor lysis syndrome and patients at high-risk for developing tumor lysis syndrome. Unfortunately, it is expensive, and unnecessary use raises costs of care. METHODS: Plan, Do, Study, Act methodology was used to decrease the inappropriate use of rasburicase. In the Plan phase, a multidisciplinary quality improvement team reviewed the rasburicase ordering process and its prescription patterns at Parkland Health and Hospital System between October 2015 and September 2017 to determine appropriate interventions for improvement. In the Do phase, interventions were deployed to improve rasburicase prescriptions. In the Study phase, the team reviewed the rasburicase orders and appropriateness from February 2018 to October 2018. During the Act phase, the interventions were found to be successful, and the process changes were solidified. RESULTS: At baseline, 65 doses of rasburicase were administered during the 2-year baseline period, 21 of these (32.3%) were inappropriate. Review of the ordering process identified pitfalls: one-click ready-to-sign order, fixed default dose, no hard-stop alert requiring physicians to review and confirm appropriate indications, and lack of secondary pharmacy review. We aimed to reduce the percentage of inappropriate rasburicase orders from a baseline of 32.3% to 10% over 3 months. In February 2018, we implemented the interventions, which resulted in reduction in inappropriate rasburicase use, with only a single inappropriate order placed in 7 months postintervention. CONCLUSION: A multidisciplinary approach and classic quality improvement methodology enabled us to reduce inappropriate rasburicase use. Straightforward electronic medical record interventions and secondary pharmacy review are effective in addressing overuse.

Purpose: There are an increased number of reports being published on rasburicase-induced methemoglobinemia recently. We aimed to identify and critically evaluate all the descriptive studies that described the rasburicase-induced methemoglobinemia, its treatment approach, and their outcomes. Methodology: PubMed and grey literature databases were searched from inception to January 2021 using search terms “rasburicase” and “methemoglobinemia” without any language and date restriction. A bibliographic search was also done to find additional studies. Only descriptive studies on Rasburicase-induced methemoglobinemia were included for our review. Two contributors worked independently on study selection, data abstraction, and quality assessment, and any disagreements were resolved by consensus or discussion with a third reviewer. Result: A total of 22 reports including 25 patients (21 male, 3 female patients, and 1 study did not specify the gender of the patient) aged from 6 to 75 years were included in the review. Immediate withdrawal of the drug and administering methylene blue, ascorbic acid, blood transfusion, and supportive oxygen therapy are the cornerstone in the management of rasburicase-induced methemoglobinemia. Conclusion: Rasburicase administration should be followed by careful monitoring of patients for any severe complication and treat it as early as possible appropriately. In a patient who presents with rasburicase-induced haemolysis or methemoglobinemia, it is often important to expect a diagnosis of G6PD deficiency unless otherwise confirmed and to avoid administering methylene blue, even though the patient is from a low-risk ethnicity for G6PDD. PROSPERO Registration number: CRD42021234132

Methemoglobinemia occurs as iron in heme is oxidized to its ferric state, resulting in a decreased ability of hemoglobin to bind and release oxygen. Rasburicase is a recombinant urate-oxidase enzyme used in the prevention of tumor lysis syndrome. Methemoglobinemia can occur as a rare complication of treatment with rasburicase, primarily in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Methylene blue, an agent used for treating methemoglobinemia, should be avoided in patients with G6PD deficiency. In patients with G6PD deficiency, methylene blue is inadequately reduced to its active form, which then causes the methylene blue to further the oxidize the hemoglobin to methemoglobin that can result in hemolysis.

Background Tumour Lysis Syndrome (TLS) is an oncological emergency caused by the rapid lysis of tumour cells. One of the biochemical abnormalities seen is a high urate level; rasburicase, a recombinant urate oxidase, can therefore be employed in both prophylaxis and treatment. Studies show significant variability in treatment regimens; its use is based on guidelines, such as those from The British Committee for Standards in Haematology (BCSH). It also carries a small risk of haemolytic anaemia, especially in those with a G6PD deficiency. Objectives This study aimed to evaluate rasburicase use within a PICU setting. We assessed whether our unit was following best practice in terms of treatment duration, drug dosage and frequency, and monitoring (both for treatment response and complications). Methods This was a retrospective study of patients receiving treatment with rasburicase in our PICU from January 2015 to May 2020. Patients receiving rasburicase were identified using electronic prescribing records. Data concerning demographics, diagnosis, clinical condition, rasburicase administration, and monitoring was then obtained from Metavision and Orion Clinical Portal. TLS risk was determined retrospectively and children classed as either having High Risk Disease (HRD), Intermediate Risk Disease (IRD), or Low Risk Disease (LRD). Results 21 patients receiving rasburicase were identified (18 with haematological malignancies, 3 with solid tumours). Data on ethnicity was available for 15/21 children, all of whom were Caucasian. Ages ranged from 9 weeks to 16 years. 5/21 had evidence of lab TLS, with 4 of these meeting the criteria for clinical TLS. 11 children were assessed to have HRD, 5 as having IRD, and 5 as having LRD. All children who had features of TLS were at high risk. 9/21 children (42.9%) received more than the 5–7 days treatment recommended by manufacturers and the BCSH, with a range from 1–21 days. Most children received 0.2 mg/kg doses with only one child receiving a dose of 2 mg/kg on one occasion. 3 children received twice daily dosing. One child died after only one dose of rasburicase; of the remainder, 100% received daily FBCs, LFTs, and U&Es while receiving rasburicase, while only 16/20 (80%) received daily urate levels to monitor response. No cases of haemolytic anaemia due to rasburicase therapy were documented, but 17/21 children required at least one red cell transfusion whilst a PICU inpatient. G6PD status was checked in only one of the children. Conclusions Significant variability in use of rasburicase exists within our PICU. Duration of rasburicase treatment varies widely and several other practices outwith those recommended by current best practice were observed, such as its use in children at low risk of developing TLS, repeated treatment courses, twice daily doses, and a child who received a >0.2 mg/kg dose. Active monitoring for haemolytic anaemia outwith daily FBCs is limited and is complicated by the frequency of children requiring blood transfusions. Awareness of this as a serious complication in a small number of children may need to be raised.

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To report a case of ribavirin-associated severe hyperuricemia in an immunocompromised patient treated for respiratory syncytial virus (RSV) infection. Summary A 21-year-old male with a past medical history of B-cell acute lymphoblastic leukemia was in full remission after allogenic bone marrow transplantation complicated with chronic graft-versus-host disease. He was hospitalized due to fever, malaise, and respiratory syndromes. A diagnosis of RSV upper respiratory tract infection complicated by secondary pneumonia was made, and oral ribavirin (600 mg in 3 divided doses daily) and intravenous levofloxacin (750 mg once daily) were initiated. On day 2 of the hospital admission, the patient’s uric acid levels had increased from a baseline of 4 to 6 mg/dL to values of 19.3 and 22.2 mg/dL after the fourth and fifth doses of ribavirin, respectively, and his serum creatinine steadily had increased from a baseline of 0.7 to 0.8 mg/dL to a value of 1.6 mg/dL. Ribavirin was discontinued after the sixth dose, and a single dose of intravenous rasburicase (7.5 mg) was administered. On day 3, the patient’s serum uric and creatinine concentrations had decreased to 4.7 mg/dL and 1.1 mg/dL, respectively. He continued to recover on antibiotics and was discharged with normal uric acid and serum creatinine levels. Conclusion We report a case of severe hyperuricemia and acute kidney injury that developed early after initiation of ribavirin for RSV infection and suspected bacterial pneumonia in an immunocompromised patient without hepatitis C, requiring ribavirin discontinuation and rasburicase administration. To our knowledge, this is the first reported case of severe hyperuricemia in a patient treated with ribavirin for RSV infection rather than chronic hepatitis C. Clinicians should be aware of the possibility of acute and severe hyperuricemia following ribavirin administration.

IntroductionVenetoclax along with hypomethylating agents (HMAs) is the new standard therapy for older patients with acute myeloid leukemia (AML) not fit for intensive frontline induction chemotherapy. Venetoclax is associated with fatal episodes of tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL), and recommendations are for its initiation for CLL and AML in the inpatient setting with close monitoring. Herein, we evaluated the safety of outpatient venetoclax ramp up when given in addition to HMAs for the treatment of AML. Methods We conducted a retrospective review of patients diagnosed with AML at our institution from 12/1/2016 until 7/1/2020. We identified patients who received HMAs and venetoclax for AML, either as frontline or relapsed/refractory therapy. Records were reviewed for evidence of laboratory or clinical tumor lysis episodes in all patients. Results Between 12/1/2016 and 7/1/2020 43 patients at our institution received venetoclax/HMA for the treatment of AML. Thirty-nine patients (91%) had venetoclax initiation and ramp up in the outpatient setting. One episode of laboratory TLS (2.5%) was identified. This patient required admission to the hospital for rasburicase and IV fluids with resolution of the laboratory effects without resultant clinical TLS. There were no episodes of clinical TLS in either group. 30-day mortality from venetoclax initiation was 0% in both groups. Conclusion Our experience with HMAs and venetoclax showed that outpatient ramp up of venetoclax is safe with a very low risk of laboratory TLS (2.5%) and no evidence of clinical TLS within our cohort.

Rasburicase can markedly and rapidly decrease uric acid (UA) levels, thereby preventing and treating tumor lysis syndrome. However, rasburicase is expensive, especially when used as per the manufacturer's recommended dosage of 0.2 mg/kg/day for up to 5 days. Numerous reports have shown that lower, and even single doses are effective in lowering UA levels but prospective randomized studies comparing low doses have not been performed.To prospectively determine the efficacy and safety of two single low doses of rasburicase in adult patients (pts) with acute leukemia and elevated plasma UA.Eligible pts aged ≥ 18 years old with acute leukemia and UA ≥ 7.5 mg/dL were randomized to receive an initial single dose of rasburicase 1.5 mg (Arm A) or 3 mg (Arm B) on day 1 in an unblinded fashion. All pts received allopurinol 300 mg daily on days 1-6.Twenty-four pts (median age 69 years; 14 males and 10 females) were enrolled in this phase 2 study (12 on each arm). Twenty pts had acute myeloid leukemia while 3 had acute lymphoblastic leukemia, and 1 had acute promyelocytic leukemia. Median initial UA level was 9.8 mg/dL. Eighty-three percent of pts in both arms achieved UA7.5 mg/dL by 24 h after therapy. Five pts (21 %; 2 from Arm A and 3 from Arm B) required additional doses of rasburicase. The majority (23/24) of pts achieved UA goals after 1-2 doses of rasburicase. None had worsening renal function. Both doses were well tolerated, and no treatment related adverse events were reported.Single doses of rasburicase (as low as 1.5-3 mg) used in addition to allopurinol were well tolerated and highly efficacious (83 % response rate) in decreasing UA levels within 24 h of administration in adult acute leukemia pts with hyperuricemia.

Spontaneous tumor lysis syndrome (STLS) is a rare oncologic emergency caused by massive cancer cell lysis or necrosis without a precipitating factor. Although tumor lysis syndrome (TLS) is most commonly associated with hematologic malignancies, a small number of cases in solid tumor malignancies have been reported. We present a case of spontaneous tumor lysis syndrome in a 77-year-old female with a widely metastatic, poorly differentiated adenocarcinoma of unknown origin. She presented in distributive shock, and laboratory testing at admission revealed acute renal failure, high anion gap metabolic acidosis, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Rasburicase and continuous renal replacement therapy were initiated, however, her condition deteriorated. Treatment was withdrawn and she died four days after admission.

Up to 18% of patients with acute myeloid leukemia (AML) present with a white blood cell (WBC) count of greater than 100,000/µL, a condition that is frequently referred to as hyperleukocytosis. Hyperleukocytosis has been associated with an adverse prognosis and a higher incidence of life-threatening complications such as leukostasis, disseminated intravascular coagulation (DIC), and tumor lysis syndrome (TLS). The molecular processes underlying hyperleukocytosis have not been fully elucidated yet. However, the interactions between leukemic blasts and endothelial cells leading to leukostasis and DIC as well as the processes in the bone marrow microenvironment leading to the massive entry of leukemic blasts into the peripheral blood are becoming increasingly understood. Leukemic blasts interact with endothelial cells via cell adhesion molecules such as various members of the selectin family which are upregulated via inflammatory cytokines released by leukemic blasts. Besides their role in the development of leukostasis, cell adhesion molecules have also been implicated in leukemic stem cell survival and chemotherapy resistance and can be therapeutically targeted with specific inhibitors such as plerixafor or GMI-1271 (uproleselan). However, in the absence of approved targeted therapies supportive treatment with the uric acid lowering agents allopurinol and rasburicase as well as aggressive intravenous fluid hydration for the treatment and prophylaxis of TLS, transfusion of blood products for the management of DIC, and cytoreduction with intensive chemotherapy, leukapheresis, or hydroxyurea remain the mainstay of therapy for AML patients with hyperleukocytosis.

Tumor lysis syndrome (TLS) is the phenomenon of metabolic derangements that typically follows the initiation of cytotoxic chemotherapy. Metabolic disturbances include hyperphosphatemia, hyperkalemia, hyperuricemia and hypocalcemia. Hematological malignancies are associated with spontaneous TLS (STLS), which is cell lysis in the absence of chemotherapy. STLS is extremely rare in chronic lymphocytic leukemia (CLL). This has been documented only once in the medical literature, making this an extraordinarily uncommon case. We present here a 68-year-old male with a history of benign prostatic hyperplasia (BPH) who is admitted for a two-week history of abdominal pain and three days of anuria, despite adequate fluid intake. Laboratory values yielded a greatly elevated leukocyte count with a lymphocytic predominance and smudge cells. Potassium, phosphorus, and uric acid were also significantly increased. EKG revealed peaked T-waves. Flow cytometry confirmed the presence of an abnormal B-cell population consistent with B-cell chronic lymphocytic leukemia, with the following markers: CD19+, CD20+, CD23+, CD5+, CD10-. He was diagnosed with CLL and treated with aggressive fluid resuscitation, allopurinol and rasburicase. The patient had another similar episode within one month. His CLL fluorescence in-situ hybridization (FISH) showed complex cytogenetics with unmutated IgVH and he was subsequently started on ibrutinib.

Patient: Female, 55-year-old Final Diagnosis: Metastatic breast cancer • tumor lysis syndrome Symptoms: Anorexia • lethargy • oliguria • weakness Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual or unexpected effect of treatment Background: Tumor lysis syndrome (TLS) represents a severe and dangerous side effect of chemotherapy. The frequency of TLS is not well known in patients with breast cancer, and there are no reports of TLS after the second or third lines of chemotherapy or immunotherapy combined with chemotherapy in these patients. Case Report: We present the case of a 55-year-old postmenopausal woman with metastatic triple-negative breast cancer who received multiple lines of chemotherapy and developed TLS after receiving combined chemoimmunotherapy. She presented to our medical center with generalized body weakness, sleepiness, anorexia, and oliguria 6 days after her first dose of combined chemoimmunotherapy with nanoparticle albumin–bound (nab)-paclitaxel (100 mg/m2) and atezolizumab (840 mg). A complete blood count on admission showed pancytopenia, with serum levels of uric acid at 17.8 mg/dL, creatinine at 3.4 mg/dL, potassium at 5.5 mEq/L, phosphorus at 5.0 mg/dL, and calcium at 9.3 mg/dL. TLS (grade 2) was diagnosed based on reported Cario-Bishop criteria, and the patient was promptly treated with intravenous hydration and a single dose of rasburicase (0.15 mg/kg). Symptoms completely resolved within 4 days, and the patient was discharged home. Conclusions: We present a case of TLS after combined therapy with atezolizumab and nab-paclitaxel in a heavily pretreated patient with metastatic triple-negative breast cancer. Medical oncologists and general practice clinicians need to be aware of the possibility of TLS, even in unlikely cases, and to recognize the clinical signs of TLS to enable prompt and appropriate management.

Tumor lysis syndrome (TLS) is a severe metabolic complication that usually occurs in patients with aggressive tumors who undergo treatment with chemotherapy. Traditionally, it was mainly associated with hematologic malignancies. However, over the past 4 decades, there have been increasing reports of TLS in solid tumors. We report a case of TLS in a patient with gastric cancer, as a complication of FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy. Our patient was a 48-year-old man with metastatic gastric adenocarcinoma who presented with altered mental status and slurred speech. On examination, he was confused and disoriented, but the rest of his examination, including vitals, was unremarkable. Laboratory findings on admission were significant for an elevated uric acid of 14.5 mg/dL, creatinine of 4.1 mg/dL, and phosphorus of 6.9 mg/dL. He had received his first cycle of FOLFOX chemotherapy 4 days prior to admission. The constellation of electrolyte abnormalities and the temporal relationship to chemotherapy led to the diagnosis of chemotherapy-induced TLS. He was treated with aggressive fluid repletion and rasburicase, following which the electrolyte derangements resolved, and he improved clinically. This case highlights the importance of early recognition of TLS in patients with gastric cancer. Initiation of early treatment can reduce the high morbidity and mortality associated with this oncologic emergency.

Therapeutic proteins can be potent agents for treating serious diseases, but in many patients these proteins provoke antibody responses that blunt therapeutic efficacy. Intravenous administration of high doses of some proteins induces immune tolerance, but the mechanisms underlying this effect are poorly understood. As a model to study tolerance induction in mice, we used rasburicase, a commercial recombinant uricase used for the treatment of hyperuricemia. Intraperitoneal (i.p.) injection of rasburicase without or with alum adjuvants induced a clear anti-rasburicase antibody response, but intravenous (i.v.) injection did not. The lack of response to i.v. rasburicase was apparently due to active immune suppression since i.v.-treated mice showed blunted antibody and reduced T cell responses to subsequent i.p. injections of rasburicase. This blunted response was associated with a decrease in rasburicase-specific B cell and T cell responses and an increase in proportion of CD4+ FoxP3+ regulatory T cells (Treg) in the spleen. We examined the number of lymphocytes in peripheral blood after rasburicase i.v. injection. Rasburicase caused a transient reduction in B and T cells, but a robust and sustained depletion of rasburicase-specific B cells. Further experiments showed that rasburicase i.v. injection decreased the number of lymphocytes and was associated with apoptosis of both B cells and activated T cells and that the enhanced percentage of Treg cells was likely mediated by a macrophage-dependent pathway. Thus, our data suggest that apoptosis and depletion of antigen-specific B lymphocytes and upregulation of Treg cells may play important roles in the immune suppression induced by intravenous administration of a therapeutic protein.

Rasburicase is a recombinant urate oxidase enzyme indicated for tumor lysis syndrome, a potential life-threatening oncologic emergency that occurs most commonly during initial chemotherapy for hematological malignancies. As a result of the defects in the physiological antioxidant pathway, erythrocytes of patients with glucose-6-phosphate dehydrogenase deficiency are not protected against the oxidizing stress exerted by hydrogen peroxide generated with the administration of rasburicase. The authors report a 14-year-old patient, diagnosed with T-cell acute lymphoblastic leukemia, who developed methemoglobinemia and hemolytic anemia with low oxygen saturation after starting steroids, hyperhydratation, and rasburicase administration. The complications resolved with supportive therapy only.

Typical hemolytic uremic syndrome (HUS) causes acute kidney injury (AKI) and serious sequelae of chronic kidney disease (CKD) in some. Hyperuricemia is a common finding in typical HUS that may contribute to kidney damage. We explored whether aggressive management of hyperuricemia with rasburicase could improve outcomes in AKI patients with typical HUS. We retrospectively analyzed medical records of children with typical HUS admitted to a tertiary center between 2005 and 2017. We compared clinical outcomes of hospitalization and 1-year post-discharge between those with rasburicase treatment (n = 13) and those without (controls, n = 29). With rasburicase treatment, hyperuricemia corrected more rapidly (median 36 vs. 120 h, p < 0.001), and hospital stays were shorter (median 9 vs. 12 days, p = 0.003) than in the controls. There was no difference in dialysis requirement. At 1-year post-discharge, the proportion of patients with impaired kidney function (estimated glomerular filtration rate < 90 mL/min/1.73 m2) was lower in the rasburicase group (7.7% vs. 41.4%, p = 0.036) than in the controls. Hypertension and proteinuria tended to be more common in the controls than in the rasburicase group. Collectively, long-term renal sequelae of impaired kidney function, proteinuria, or hypertension at a 1-year follow-up was less common in the rasburicase group than in the controls (7.7% vs. 62.1%; p = 0.001). Children with typical HUS treated with rasburicase had shorter hospital stays and less long-term sequelae at 1-year post-discharge than those who were not treated with rasburicase. These results support the use of rasburicase to prevent CKD in pediatric patients with typical HUS-associated AKI.

Tumor lysis syndrome (TLS) occurs in rapidly proliferating tumor cells, either spontaneously or after cytotoxic therapy. It has been well-documented in hematological diseases but is extremely rare in solid neoplasms, particularly in prostate cancer (PRCA). In the presence of risk factors, it can cause metabolic disturbances and be potentially fatal. We searched PubMed, Medline, ScienceDirect, and Scopus for "tumor lysis syndrome" and "prostate cancer" and conducted a systematic review with a pooled analysis for the published literature and cases from our institution. Twenty-two TLS cases were identified (18 published in the literature and four cases from our institution). The patients' median age was 68 years (range 16-82), and most cases were prostate adenocarcinoma. The median prostate-specific antigen (PSA) was 374 (range 66.7-10,867). Ten cases (45.5%) had spontaneous TLS (STLS) while 12 cases (54.5%) were treatment-related (TTLS). All patients had elevated lactate dehydrogenase (LDH) with other biochemical variables, and all underwent aggressive supportive therapy. Eleven patients underwent hemodialysis, 12 patients received rasburicase, while three patients received allopurinol. The mortality rate was 75% among 12 cases of TTLS, and it was 30% of the 10 cases with STLS. Among patients with PRCA, both TTLS and STLS linked to very high mortality. Early identification of TLS would substantially attain improved survival outcomes. Hence, physicians should consider TLS as a differential diagnosis when evaluating AKI and electrolyte abnormalities, particularly in patients with metastatic PRCA and high disease burden, even before the initiation of cytotoxic therapy.

Rasburicase was introduced to treat hyperuricemia secondary to tumor lysis syndrome. Because of severe hemolytic anemia, a blood smear was requested and showed hemighosts, revealing G6PD deficiency. Erythrocyte morphology is a key tool in laboratory hematology.

Background: Tumour lysis syndrome (TLS) occurs when lysis of malignant cells causes electrolyte disturbances and potentially organ dysfunction. Guidelines recommending preventive therapy according to TLS risk are based on low-quality evidence.Objectives: The primary objective was to characterize utilization of TLS preventive strategies through comprehensive description of current practice. Secondary objectives were to determine TLS incidence, to compare use of preventive strategies among intermediate- and high-risk patients, and to describe TLS treatment strategies.Methods: This retrospective chart review examined data for patients with newly diagnosed hematologic malignancy who were admitted to an oncology centre and/or affiliated intensive care unit between October 2015 and September 2016 in Toronto, Ontario, Canada. Results: Fifty-eight patients (29 at intermediate risk, 29 at high risk) were eligible for inclusion. Use of preventive allopurinol, IV bicarbonate, and furosemide was similar between groups. Rasburicase was more frequently used for high-risk patients (3% [1/29] of intermediate-risk patients versus 36% [9/25] of high-risk patients; p = 0.003). In 4 (14%) of the intermediate-risk patients and 2 (8%) of the high-risk patients, TLS developed during the admission. TLS was observed in 10% (1/10) of patients who received preventive rasburicase and 11% (5/44) of those who did not (p > 0.99), and in 9% (4/45) of patients who received preventive IV bicarbonate and 25% (2/8) of those who did not (p = 0.22). Treatment strategies included rasburicase, IV bicarbonate, furosemide, and renal replacement therapy.Conclusions: In this retrospective chart review, rasburicase was more commonly used for high-risk patients, whereas the use of other agents was similar between risk groups. This pattern of use is inconsistent with guidelines, which recommend that all high-risk patients receive rasburicase. There was no difference in TLS incidence between patients who did and did not receive preventive rasburicase or IV bicarbonate. Further prospective studies are needed to inform management of patients with malignancies who are at intermediate or high risk of TLS.RÉSUMÉContexte : Le syndrome de lyse tumorale (SLT) se produit lorsque la lyse de cellules malignes provoque des perturbations électrolytiques et la dysfonction potentielle d’un organe. Les lignes directrices préconisant une thérapie préventive basée sur le risque de SLT se fondent sur des éléments de preuve de piètre qualité.Objectifs : L’objectif principal consistait à décrire l’adoption des stratégies de prévention du SLT en décrivant précisément la pratique actuelle. Les objectifs secondaires consistaient, quant à eux, à déterminer l’incidence du SLT, à comparer l’utilisation des stratégies de prévention pour les patients présentant un risque élevé et moyen et à décrire les stratégies de traitement du SLT.Méthodes : Cet examen rétrospectif a permis d’examiner les données de patients ayant récemment reçu un diagnostic d’hémopathie maligne et ayant été admis dans un centre d’oncologie ou une unité de soins intensifs affiliée, entre octobre 2015 et septembre 2016 à Toronto (Ontario), au Canada.Résultats : Cinquante-huit patients (29 présentant un risque moyen et 29 un risque élevé) étaient admissibles. L’utilisation d’allopurinol à titre préventif, de bicarbonate par voie intraveineuse et de furosémide était similaire d’un groupe à l’autre. Le rasburicase était plus fréquemment utilisé pour les patients présentant un risque élevé (3 % [1/29] de patients présentant un risque moyen contre 36 % [9/25] de patients présentant un risque élevé; p = 0.003). Quatre (14 %) patients présentant un risque moyen et deux (8 %) présentant un risque élevé ont développé un SLT pendant l’admission. Le SLT a été observé chez 10 % (1/10) des patients ayant reçu du rasburicase à titre préventif et chez 11 % (5/44) des patients qui n’en avaient pas reçu (p > 0,99); il a aussi été observé chez 9 % (4/45) des patients ayant reçu du bicarbonate par voie intraveineuse à titre préventif et chez 25 % (2/8) des patients qui n’en avaient pas reçu (p = 0.22). Les stratégies de traitement comprenaient le rasburicase, le bicarbonate par voie intraveineuse, le furosémide et la thérapie de remplacement rénal.Conclusions : Dans cet examen rétrospectif des dossiers, l’usage du rasburicase était plus fréquent pour les patients présentant un risque élevé, tandis que celui d’autres agents était similaire entre les groupes à risque. Ce schéma d’utilisation n’est pas conforme aux lignes directrices, qui recommandent que tous les patients présentant un risque élevé reçoivent du rasburicase. Aucune différence n’est apparue dans l’incidence du SLT parmi les patients ayant reçu du rasburicase ou du bicarbonate par voie intraveineuse à titre préventif et parmi ceux qui n’en avaient pas reçu. Davantage d’études prospectives sont nécessaires pour mieux connaitre la gestion des patients à haut risque ou ceux qui présentent des risques moyens de SLT, mais qui ont des malignités.

Background Uric acid (UA) is a plasmatic antioxidant that has possible effects on blood pressure. The effects of UA on endothelial function are unclear. We hypothesize that endothelial function is not impaired unless significant UA depletion is achieved through selective xanthine oxidase inhibition with febuxostat and recombinant uricase (rasburicase). Methods and Results Microvascular hyperemia, induced by iontophoresis of acetylcholine and sodium nitroprusside, and heating-induced local hyperemia after iontophoresis of saline and a specific nitric oxide synthase inhibitor were assessed by laser Doppler imaging. Blood pressure and renin-angiotensin system markers were measured, and arterial stiffness was assessed. CRP (C-reactive protein), allantoin, chlorotyrosine/tyrosine ratio, homocitrulline/lysine ratio, myeloperoxidase activity, malondialdehyde, and interleukin-8 were used to characterize inflammation and oxidative stress. Seventeen young healthy men were enrolled in a randomized, double-blind, placebo-controlled, 3-way crossover study. The 3 compared conditions were placebo, febuxostat alone, and febuxostat together with rasburicase. The allantoin (μmol/L)/UA (μmol/L) ratio differed between sessions (P, info:eu-repo/semantics/published

Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency, characterized by a constellation of hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia. The spectrum ranges from patients who are asymptomatic to those who go into cardiac arrest and die. Prompt recognition and initiation of treatment by emergency physicians are key, especially in the early stages of the syndrome. This case-based review presents an overview of the key points in pathophysiology, diagnosis, and management of TLS that are key to emergency physicians.