Dose Of Rasburicase Research Articles

Effectiveness of a Single Fixed Dose of 3 mg Rasburicase for the Prevention and Management of Hyperuricemia in Tumor Lysis Syndrome in Adults With Cancer.

Tumor lysis syndrome (TLS) is a critical and potentially fatal complication linked to specific types of cancer. Rasburicase stands as a crucial medication necessary for the prevention and treatment of hyperuricemia, a condition commonly associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed-dose strategy of 3 mg rasburicase was used in many adult cancer patients in our center. The objective of this study was to assess the effectiveness of a fixed dose of 3 mg rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. We conducted a retrospective, observational cohort study between March 2020 and February 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum uric acid (UA) levels at 24 and 48 hours after treatment, with the aim of achieving and maintaining normal UA levels. Seventeen patients in the treatment group and 20 patients in the prevention group were included. In the treatment group, 15 (88%) patients had normalization of serum UA, which is considered to be <7 mg/dL (median: 4.48 mg/dL) at 24 hours, and 16 (94%) patients had achieved normal UA at 48 hours (median: 2.78 mg/dL) after receiving the rasburicase dose. In the prevention group, all 20 (100%) patients achieved normal UA at 24 hours after receiving the rasburicase dose. Based on these findings, a single fixed dose of 3 mg rasburicase is effective for preventing and managing hyperuricemia associated with TLS in high-risk patients.

A retrospective review of rasburicase utilization in pediatric and adult patients across a large health system.

This study aimed to characterize rasburicase dosing and duration. Secondary objectives included characterizing the indication of rasburicase and identifying the utilization of prophylactic therapy for tumor lysis syndrome (TLS). This retrospective review included patients 0 to 89 years old admitted between 1 January 2021 and 31 December 2021, and received at least one dose of rasburicase. Patients were excluded if they were >89 years old, pregnant, lactating, or received rasburicase outpatient. A total of 192 patients, 176 adults and 16 pediatric patients were included in the retrospective review. Of the total population, 184 received a fixed dose of rasburicase and 8 patients received a weight-based dose (0.15 mg/kg/dose) of rasburicase. The average dose administered was 3.4 mg for fixed and 2.99 mg for weight-based dosing. Nearly half (49.5%) the patients received rasburicase for an elevated uric acid but did not meet Cairo-Bishop criteria for TLS. Only 42.2% received at least one dose of allopurinol within 5 days prior to rasburicase and 18.8% received aggressive hydration within 72 h prior to rasburicase. The majority of rasburicase administered was ordered as fixed dose for a uric acid level ≥7.5 mg/dL. Most patients did not meet criteria for laboratory or clinical TLS and less than half the patients received prophylactic allopurinol and/or aggressive hydration. These study results are supported by recent literature for fixed dose rasburicase as a safe and economical dosing strategy compared to weight-based dosing.

Treatment with Rasburicase in Hospitalized Patients with Cardiorenal Syndrome: Old Treatment, New Scenario.

Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m2 (p = 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function.

Rasburicase dose optimization for tumor lysis syndrome management in a network of community oncology practices.

Single, fixed-dose rasburicase administration has been evaluated as an effective strategy in the management of hyperuricemia in the hospital setting, but this has not yet been described within ambulatory community oncology practices. The objective of this study is to evaluate and optimize the dosing strategy for rasburicase in the management of tumor lysis syndrome (TLS)-associated hyperuricemia in The US Oncology Network (The Network). A network-wide guideline was revised to standardize rasburicase dosing from a previous recommended fixed doses of 4.5 or 7.5 mg to either 3 or 6 mg for outpatient rasburicase use in management and prevention of TLS. The primary outcome evaluated mean dose of rasburicase among all patients before and after guideline revision. A retrospective chart review evaluated secondary endpoints. The primary analysis included 291 patients (128 pre-revised and 163 post-revised guideline implementation). The primary outcome, mean rasburicase dose, was reduced in the post-revision compared to the pre-revision population (mean 6.2 mg pre vs. 4.5 mg post, p < 0.00001) resulting in a reduced cost per rasburicase dose of $974. Fifty patients were included for the secondary analysis. Guideline concordance was identified in 12 (48%) and 16 patients (64%), and uric acid <8 mg/dL post-rasburicase administration occurred in 14 (56%) and 16 patients (64%) before and after guideline revision, respectively. Guideline revision and electronic health record modification resulted in a 27% reduction in the mean rasburicase dose and a 50% reduction in repeat rasburicase dosing without a negative impact on clinical efficacy.

#4916 A PILOT STUDY ON THE BENEFICIAL EFFECT OF RASBURICASE IN THE PREVENTION OF ACUTE RENAL FAILURE IN PATIENTS WITH CARDIORENAL SYNDROME

Abstract Background and Aims Uricase metabolizes uric acid into allantoin, a soluble compound that is easily excreted in the urine. Acute hyperuricemia is associated with endothelial injury and vasoconstriction, favoring acute renal failure. Preliminary studies show the protective role of lowering uric acid in cardiac patients. Method Pilot study conducted in patients with cardiorenal syndrome and hyperuricemia (&amp;gt;9 mg/dl). All received a single dose of rasburicase (0.20 mg/kg/day in the first 9 patients or a fixed dose of 6 mg in 14 patients) evaluating its effect on renal function and the need for renal replacement therapy. Results Twenty-three patients aged 68 ± 14 years were included, 14 men and 9 women, 87% hypertensive, 35% diabetic, 17% with liver disease, and 26% with cancer. Baseline: mean LVEF 40±14.1% (13-63), pro-BNP 19880±14000ng/l, basal Cr 1.55±0.58 mg/dl, uric acid 14.1±2.26, phosphorus 5 .3±1.6 mg/dl and CRP 7±8 mg/l. The evolution of renal function after treatment is shown in Table 1. In all patients, uric acid after rasburicase decreased to 0.5 mg/dl. There were no differences in renal function, RRT, and hospitalization between patients who received a dose of 0.20 mg/kg/day or 6 mg iv. Only 3 patients required RRT for 21±23 hours, with recovery from acute renal failure. Comparing the patients who required RRT versus those who did not, these presented higher baseline uric acid levels: 16.5±2.5 vs 13.7±1.1 mg/dl, P = .049, and there were no differences in LVEF. pro-BNP and previous renal function. One patient died during the hospital stay due to terminal CHF and sepsis, but having recovered kidney function. Conclusion Rasburicase administration may prevent established renal failure in patients with cardiorenal syndrome and hyperuricemia. Early treatment, avoiding very high levels of hyperuricemia, could be more effective in reducing the need for renal replacement therapy.

Efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis

Objective: To explore the efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis. Methods: A cohort study. The clinical data of patients with refractory chronic gouty arthritis who were treated with rasburicase at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between January 2021 and July 2022 were retrospectively analyzed. Refractory chronic gouty arthritis was defined as serum uric acid (sUA)>360 μmol/L and urate volume>10 cm3 under dual-energy computed tomography after tolerable maximal oral urate-lowering therapy for at least 3 months. The administration of low-dose rasburicase was applied intravenously with total dosage ranging from 4.5 to 7.5 mg each dose, at 4-week intervals for a maximum of three doses. Efficacy was evaluated by the changes of sUA level, tophus and urate volume. Results: A total of 22 patients were included for analysis, with 95.4% (21/22) male, the mean age was (44±15) years, and the median duration of gout was 11 (6-15) years. The mean sUA at baseline was (667±112) μmol/L. The levels of sUA significantly decreased after each dose of rasburicase (P<0.001), and the median reduction of sUA after each dose of rasburicase was 568 (471-635), 187 (66-335) and 123 (49-207) μmol/L, respectively. At week 12, nine patients (40.9%) exhibited sUA<360 μmol/L and tophus disappeared in one patient. The urate volume significantly decreased at week 12 when compared with that before the first dose of rasburicase in all the patients [40 (16-172) cm3 vs 17 (7-134) cm3, P<0.001], with a median reduction rate of 41.6% (22.9%-58.5%). The everall safety of rasburicase was good, and no serious adverse reactions occurred. Conclusions: Low-dose rasburicase is well-tolerated and effective for decreasing the urate burden in patients with refractory chronic gouty arthritis. Further prospective randomized controlled trials are needed to validate these findings.

Serum Albumin fused Flt3L expands a tolDC compartment and amplifies tolerogenic antigen immunotherapy for the prevention of pathogenic anti-drug antibody responses

Abstract From antibodies to enzyme replacement therapies, biologics and protein drugs have become a major part of the medical market and revolutionized medicine. Repeated administration of many of these drugs, however, leads to humoral responses and potentially drug failure via neutralization, clearance, or immune related infusion reactions. Once pathogenic anti-drug antibodies are formed, patients must take broad immunosuppressive drugs, undergo continuous B cell depletion, or discontinue treatment entirely. Currently, no drugs are approved by the FDA to prevent the induction of anti-drug antibodies. Herein, we characterize the effect of our engineered cytokine, Flt3L-SA, in vivoand demonstrate how our molecule expands the dendritic cells while enhancing a tolerogenic, TGFβ expressing subpopulation. We then leverage these dendritic cells to attenuate the antibody response to the highly immunogenic drug Rasburicase and ultimately reduce antibodies by 100-fold when administered as part of a tolerogenic regime with low dose Rasburicase. We also show how this reduction in antibodies results in fewer and less severe infusion reactions upon final challenge, evidencing both a reduction in the antibody response as well as pathology. Future work will aim to determine the exact mechanism by which this tolerance is achieved as well as demonstrate efficacy in the context of a wide range of extremely immunogenic therapies, including enzyme replacement therapeutics for lysosomal storage disorders and AAV therapies. Supported via the Chicago Immunoengineering Innovation Center and the Alper Family Foundation

A phase II study to evaluate the efficacy of low-dose rasburicase (1.5mg) in adolescent and adult acute leukemia and high-grade lymphomas with tumor lysis syndrome

The FDA recommended dose of rasburicase 0.2 mg/kg/day till the resolution of TLS or up to 5 days, might be in excess and is prohibitively expensive. The quality of evidence supporting low dose rasburicase is limited. The objective is to study the plasma uric acid response rate. This is a single center, non-randomised phase II study. Duration is 10 June 2017 till 30 July 2019. Study setting is at Adult Hematolymphoid Unit, Tata Memorial Center. Participants are patients with acute leukemia and high-grade lymphomas aged >/=18 years, with ECOG PS of 0–3, with either laboratory or clinical TLS. Rasburicase was administered at fixed-dose of 1.5 mg. The subsequent doses (1.5 mg each dose) were administered only if plasma UA levels did not decline by >50% on day 2, at the physician’s discretion. We demonstrate that a low-dose rasburicase strategy leads to rapid and sustained reductions of uric acid in about 52% patients.

The efficacy and cost-impact of rasburicase 3 mg versus 6 mg for the management of tumor lysis syndrome: A multicenter analysis.

Purpose: Hyperuricemia is a complication arising from tumor lysis syndrome (TLS). Literature has shown that a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid (UA) levels were ≤12 mg/dL. Here, we present a multi-center analysis rasburicase utilization and its effect on healthcare costs. Methods: This is a multi-center, retrospective analysis of adult cancer patients who were admitted to Methodist Le Bonheur Healthcare hospitals and received rasburicase from February 2020 to February 2021. The primary endpoint was to test whether rasburicase 3 mg had similar rates of uric acid normalization (defined as uric acid ≤7.5 mg/dL) within 24 h as a dose of 6 mg. Results: Seventy-nine patients were included in the study. While the baseline uric acid was lower in the 3 mg arm compared to the 6 mg arms, there was no difference in the uric acid normalization at 24 h between the 3 mg arm (95%) and 6 mg arm (82%) (p = 0.134). A cost-savings of over $300,000 annually can be achieved with the proposed protocol. Conclusion: A single, fixed rasburicase dose of 3 mg was effective in normalizing uric acid levels within 24 h, and is associated with significant cost-savings.

Glucose-6-phosphate dehydrogenase deficiency presenting with rhabdomyolysis in a patient with coronavirus disease 2019 pneumonia: a\xa0case report

BackgroundGlucose-6-phosphate dehydrogenase deficiency is a rarely recognized predisposing factor for rhabdomyolysis. Rhabdomyolysis with coronavirus disease 2019 has been increasingly seen during the pandemic. We report the uncommon occurrence of coronavirus disease 2019 pneumonia, severe rhabdomyolysis, and acute renal failure in the setting of glucose-6-phosphate dehydrogenase deficiency.Case presentationA 19-year-old African American male presented with myalgias, diaphoresis, and dark urine. Testing for severe acute respiratory syndrome coronavirus 2 was positive. He had severe rhabdomyolysis with creatine kinase levels up to 346,695 U/L. He was oliguric and eventually required hemodialysis. Progressive hypoxemia, methemoglobinemia, and hemolytic anemia occurred following one dose of rasburicase for hyperuricemia. Glucose-6-phosphate dehydrogenase deficiency was diagnosed. Full recovery followed a single volume exchange transfusion and simple packed red blood cell transfusions.ConclusionsGlucose-6-phosphate dehydrogenase deficiency may predispose individuals to rhabdomyolysis due to severe acute respiratory syndrome coronavirus 2, presumably due to altered host responses to viral oxidative stress. Early screening for glucose-6-phosphate dehydrogenase deficiency can be useful for management of patients with rhabdomyolysis.

Single-Dose Rasburicase Might Be Adequate To Overcome Tumor Lysis Syndrome In Hematological Malignancies

IntroductionTumor 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. Patients and MethodsEighty-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. ResultsWe 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. ConclusionRasburicase 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.

Efficacy and Safety of Two Comparable Single Low Doses of Rasburicase Followed By Allopurinol in Adult Patients with Acute Leukemia

BACKGROUND: Hyperuricemia is a major cause of tumor lysis syndrome (TLS) related acute kidney injury. Certain hematologic malignancies (acute leukemia, high-grade lymphoma) pose a high-risk for spontaneous and chemotherapy-induced TLS. Allopurinol, a xanthine oxidase inhibitor, can inhibit formation of new uric acid (UA), but it does not eliminate the already formed UA. Alternatively, urate oxidases like rasburicase (ELITEK®, Sanofi Genzyme) can markedly and rapidly decrease UA levels through oxidation of UA to allantoin and hydrogen peroxide. In a phase III trial, rasburicase therapy more rapidly controlled UA than allopurinol in adults with hyperuricemia or at high-risk for TLS. However, rasburicase is expensive, especially when used as per the manufacturer's recommended dosage of 0.2mg/kg/day for up to 5 days. Numerous reports have shown that lower, and even single, doses are effective in lowering UA levels.OBJECTIVES: To determine the efficacy and safety of two single low doses of rasburicase (1.5mg vs. 3mg) in adult patients with acute leukemia and elevated plasma uric acid ≥ 7.5mg/dL.METHODS: Patients ≥ 18 years treated inpatient for acute leukemia with UA ≥ 7.5 mg/dL and at risk for TLS were randomized to one of two treatment arms (ClinicalTrials.gov Identifier: NCT01564277). Patients received either rasburicase 1.5mg (Arm A) or rasburicase 3mg (Arm B) intravenously over 30 minutes on day 1 in an open-label and unblinded fashion. All patients received allopurinol 300mg daily on days 1-6 (dose reduced for reduced calculated creatinine clearance). Plasma samples for UA evaluation were collected at baseline, and at approximately 4, 24, 48, 72, 96, 120, 144 hours after the Day 1 dose of rasburicase. If UA > 7.5 mg/dL at 24 or 48 hours, then additional dose of rasburicase could be administered (1.5mg for Arm A, 3mg for Arm B). Primary endpoint was the response rate of obtaining UA ≤ 7.5mg/dL within 24 hrs of rasburicase treatment. Secondary endpoints included rate of patients that maintained UA ≤ 7.5 mg/dl on days 2-6, rate of patients who required additional rasburicase doses, rate of patients experiencing significant worsening of renal function, as well as safety of low single-dose rasburicase. Patients were followed for adverse events (AE; as defined in CTCAE version 4) for up to 30 days after last dose of rasburicase or resolution of drug-related AE.RESULTS: 24 patients were enrolled on this phase 2 study (12 on each arm; Table 1). 83% of patients in both arms achieved UA response by 24 hours (Table 2). Two pts in Arm A (baseline UA: 14.2 and 17.6 mg/dL) and three pts in Arm B (baseline UA: 15.3, 10.2, 11.9 mg/dL) were given one additional rasburicase dose. Only one pt (from Arm A) had UA > 7.5 mg/dL between days 2-6. None of the patients had doubling of their baseline serum creatinine or required hemodialysis support. Average decrease in UA was lower in Arm A as compared to Arm B (5.5 vs. 6.8 mg/dL). AE data from 21 pts showed that both low doses were overall well tolerated and most toxicities were unrelated to rasburicase. No patient deaths were attributed to rasburicase. An ad-hoc analysis showed significant rasburicase specific cost benefits using either of the low doses as compared to FDA approved dosage and other studied regimens (Table 3).CONCLUSIONS: Single low doses of rasburicase (1.5mg and 3mg) plus allopurinol are well tolerated and appear to be equally efficacious in decreasing UA levels in adult patients with leukemia at high risk for TLS. If baseline UA is elevated (>12 mg/dL), a 3mg or higher dose of rasburicase might be preferable. Preliminary cost analysis profiling favors the use of the low dose rasburicase. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

English

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

A retrospective observational study of a low fixed-dose rasburicase protocol for the treatment of tumor lysis syndrome in adults.

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. 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. Mean UA reduction in the 1.5 mg group (n = 49) from baseline to 24 hours was 2.88 ± 0.88 mg/dL (p < 0.0001) and 4.83 ± 1.39 mg/dL (p < 0.0001) in the 3 mg group (n = 105). A subgroup analysis of patients who received per protocol initial doses of rasburicase showed a mean reduction in UA from baseline to 24 hours of 2.83 ± 0.62 mg/dL in the 1.5 mg group (n = 42) and 6.12 ± 1.87 mg/dL in the 3 mg group (n = 42). Using a low fixed-dose approach resulted in a cost-savings of $138,077.30 annually. 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.

A phase 2 trial of single low doses of rasburicase for treatment of hyperuricemia in adult patients with acute leukemia

BackgroundRasburicase 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. ObjectivesTo prospectively determine the efficacy and safety of two single low doses of rasburicase in adult patients (pts) with acute leukemia and elevated plasma UA. MethodsEligible 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. ResultsTwenty-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 UA < 7.5 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. ConclusionsSingle 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.

METASTATIC SMALL CELL NEUROENDOCRINE CARCINOMA MANIFESTING AS SPONTANEOUS TUMOR LYSIS SYNDROME

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Tumor lysis syndrome is termed oncologic emergency that results from massive cell lysis. It can happen even before initiation of chemotherapy and can be an initial manifestation of malignancy itself which is termed as spontaneous tumor lysis syndrome (STLS). It is rare and is commonly associated with hematological malignancy where the proliferation and tumor burden are high. Solid tumors manifesting as STLS is extremely rare[1] CASE PRESENTATION: 62-year-old male presented after a fall to emergency department with facial and scalp laceration. Focused assessment with sonography for trauma showed multiple hypoechoic lesions of the liver. Labs showed severe metabolic acidosis with labs showing uric acid 9.9, potassium 5.7, bicarbonate 8, phosphate 8.4, creatine of 1.4, with base line creatine of 0.8, corrected calcium 8.4, Aspartate transaminase 664, Alanine transaminase 213, total bilirubin 10.1, direct bilirubin 5.3, Lactate dehydrogenase 12,677, INR 1.7, lactic acid 17. CT chest abdomen pelvis with intravenous contrast revealed small metastatic nodules in lung less than 5 mm, multiple masses in liver suggestive of metastasis, bilateral adrenal enlargement, irregularity in prostate and seminal vesicles, osteoblastic lesions in L4 lumbar vertebra. He was oliguric with no improvement with intravenous fluids requiring dialysis. A dose of rasburicase given for STLS which improved uric acid levels. He was admitted 2 weeks before fall for urinary retention requiring foley for 5 days. Prostate specific antigen (PSA) levels during present admission slightly elevated at 9. Liver biopsy showed small cell neuroendocrine carcinoma and immunohistochemical stain is negative for PSA. He developed multiorgan failure and family decided not proceed with any further interventions given poor prognosis. Primary location presumed to be prostate based on clinical findings and imaging. DISCUSSION: STLS in solid tumors is not common[2]. Close monitoring of electrolytes and kidney function is needed in patients with suspected extensive metastasis even before pathological diagnosis[2]. Although labelled as an oncologic emergency every physician need to be aware of STLS as this is true fatal emergency and can improve outcomes with timely initiation of treatment with IV fluids, rasburicase and dialysis if necessary PSA will not be significantly elevated in neuroendocrine differentiation and tumor stains will negative for PSA due to differentiation of prostate epithelium to neuroendocrine cells. CONCLUSIONS: High index of suspicion is necessary in diagnosis of STLS. Timely initiation of treatment improves patient outcome. STLS in solid tumors have poor prognosis Reference #1: 1. Serling-Boyd N, Quandt Z, Allaudeen N. Spontaneous tumor lysis syndrome in a patient with metastatic prostate cancer. Molecular and clinical oncology. 2017;6(4):589-592. doi:10.3892/mco.2017.1186 Reference #2: 2. Sommerhalder D, Takalkar AM, Shackelford R, Peddi P. Spontaneous tumor lysis syndrome in colon cancer: a case report and literature review. Clinical case reports. 2017;5(12):2121-2126. doi:10.1002/ccr3.1269 DISCLOSURES: No relevant relationships by Chandrakala Dadeboyina, source=Web Response No relevant relationships by Pushpa Khanal, source=Web Response No relevant relationships by JOYSON POULOSE, source=Web Response No relevant relationships by Harshil Shah, source=Web Response No relevant relationships by LITTY THOMAS, source=Web Response

Evaluation of the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies

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.

Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients

BackgroundTumor 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. Patients and MethodsWe 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 acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration. ResultsFifty-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. ConclusionSingle-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.

Assessment of rasburicase utilization for tumor lysis syndrome management in pediatric and adult patients in the inpatient and outpatient settings.

At Wake Forest Baptist Health, an adult tumor lysis syndrome pocket card was created in order to optimize management of tumor lysis syndrome and outline specific recommendations for the use of rasburicase. Due to the increased use of rasburicase at our institution and its cost, the purpose of this study was to evaluate the utilization of rasburicase for the management of tumor lysis syndrome in pediatric and adult patients in the inpatient and outpatient settings. This was an observational, single-center, non-randomized, retrospective chart review conducted between September 2018 and August 2019. The primary objective was to evaluate the utilization of rasburicase and appropriateness for the management of tumor lysis syndrome in pediatric and adult patients based on the Wake Forest Baptist Health tumor lysis syndrome pocket card. The secondary objectives were to assess response to prophylactic and treatment doses of rasburicase and to quantify drug cost versus expense of rasburicase utilization. Overall, 64 patients (57 adults and 7 pediatric patients) were included in the study. Rasburicase use for tumor lysis syndrome indication adhered to the pocket card 64% of the time. Appropriate fluids and/or allopurinol were initiated in only 34% of patients. For monitoring, 80% of patients had all necessary tumor lysis syndrome laboratory values collected after rasburicase administration. All 11 patients (17%) who received rasburicase in the outpatient setting did not have follow-up labs collected. Of the patients who had tumor lysis syndrome laboratory values collected post rasburicase, 39% were appropriately timed to accurately assess efficacy of rasburicase with the median time of laboratory monitoring after rasburicase being 6.5 h. Response was observed with rasburicase 3 mg (92%), 6 mg (100%), and weight-based dosing (100%). The wholesale acquisition cost per patient was $5203 (1101-10,406). The potential cost savings of using the 3 mg dose versus the 6 mg dose for the patients who did not meet tumor lysis syndrome treatment recommendations based on the Wake Forest Baptist Health pocket card was estimated to be $36,419.46. There are several opportunities for improvement in tumor lysis syndrome management and rasburicase utilization at our institution. This study will lead to the implementation of formal restrictions for rasburicase use and selection of rasburicase dose. Updating the rasburicase order panel to include appropriate prophylaxis and require input of uric acid level, populating pertinent tumor lysis syndrome laboratory values on the order verification screen for pharmacists to appropriately assess if rasburicase meets the institution restriction criteria, and providing education to providers on the appropriate ordering and timing of labs.

QIM20-119: The Efficacy of Cost-Effective Fixed Dose of Rasburicase Compared to Weight-Based Dose in Treatment and Prevention of Tumor Lysis Syndrome (TLS)

QIM20-119: The Efficacy of Cost-Effective Fixed Dose of Rasburicase Compared to Weight-Based Dose in Treatment and Prevention of Tumor Lysis Syndrome (TLS)