The Experts below are selected from a list of 393 Experts worldwide ranked by ideXlab platform
Mitchell S Cairo - One of the best experts on this subject based on the ideXlab platform.
-
a clinical and economic comparison of Rasburicase and allopurinol in the treatment of patients with clinical or laboratory tumor lysis syndrome
Clinical Lymphoma Myeloma & Leukemia, 2017Co-Authors: Mitchell S Cairo, Stephen C Thompson, Krishna Tangirala, Michael EaddyAbstract:Abstract Background The aim of the study was to compare reductions in uric acid (UA), length of stay (LOS), and hospitalization costs in patients with tumor lysis syndrome (TLS) treated with Rasburicase or allopurinol. Patients and Methods This retrospective study of administrative data included hospitalized pediatric and adult patients who had clinical or laboratory TLS and received Rasburicase or allopurinol. Each Rasburicase-treated patient was propensity score-matched with 4 allopurinol-treated patients. Mean changes in UA within ≤ 2 days of treatment initiation were determined. Economic outcomes included mean number of days in the intensive care unit (ICU), total LOS, costs/hospitalization, and costs/percentage change in UA. Results Twenty-six Rasburicase-treated patients were matched with 104 allopurinol-treated patients. Reduction in plasma UA was 5.3 mg/dL greater for patients treated with Rasburicase than for patients treated with allopurinol ( P P P = .02). Total costs per patient were $20,038 lower for patients treated with Rasburicase than for patients treated with allopurinol ( P P Conclusion In this analysis of TLS patients who received care in real-world settings, Rasburicase versus allopurinol was significantly more effective in treating hyperuricemia and was associated with significantly shorter ICU and overall hospital stays and lower total inpatient costs.
-
recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome tls in adults and children with malignant diseases an expert tls panel consensus
British Journal of Haematology, 2010Co-Authors: Mitchell S Cairo, Bertrand Coiffier, Alfred Reiter, Anas YounesAbstract:Tumour lysis syndrome (TLS) is a life-threatening oncological emergency characterized by metabolic abnormalities including hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. These metabolic complications predispose the cancer patient to clinical toxicities including renal insufficiency, cardiac arrhythmias, seizures, neurological complications and potentially sudden death. With the increased availability of newer therapeutic targeted agents, such as Rasburicase (recombinant urate oxidase), there are no published guidelines on the risk classification of TLS for individual patients at risk of developing this syndrome. We convened an international TLS expert consensus panel to develop guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. Risk factors included biological evidence of laboratory TLS (LTLS), proliferation, bulk and stage of malignant tumour and renal impairment and/or involvement at the time of TLS diagnosis. An international TLS consensus expert panel of paediatric and adult oncologists, experts in TLS pathophysiology and experts in TLS prophylaxis and management, developed a final model of low, intermediate and high risk TLS classification and associated TLS prophylaxis recommendations.
-
guidelines for the management of pediatric and adult tumor lysis syndrome an evidence based review
Journal of Clinical Oncology, 2008Co-Authors: Bertrand Coiffier, Ching-hon Pui, Anas Younes, Arnold J Altman, Mitchell S CairoAbstract:Purpose Tumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS. Methods A panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used. Results New guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic Rasburicase in high-risk patients, hydration plus allopurinol or Rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involve...
-
Rasburicase a new approach for preventing and or treating tumor lysis syndrome
Current Pharmaceutical Design, 2005Co-Authors: O Bessmertny, Lauren M Robitaille, Mitchell S CairoAbstract:Tumor lysis syndrome (TLS) is an oncologic emergency requiring prompt attention to the management of potentially life-threatening metabolic derangements. Hyperuricaemia is one of the prominent features of TLS which, if not adequately prevented or treated, may lead to renal failure, requiring dialysis. Conventional management of hyperuricaemia involved the use of aggressive hydration, urinary alkalinization and allopurinol. Despite these measures, as many as 14.1% of high-risk patients may still develop renal failure. With the advent of newer agents such as Rasburicase, the paradigm of TLS management has shifted towards risk stratification and the use of Rasburicase in conjunction with hydration in patients at high risk for TLS. The advantage of Rasburicase over allopurinol is its rapid onset of action, lack of need for urine alkalinization, which may worsen hyperphosphataemia and a satisfactory safety profile. Overall, Rasburicase offers a safe and more effective alternative to allopurinol in patients at highest risk for TLS. Some of the unanswered questions requiring further investigation with regard to Rasburicase use include the optimal number of doses needed, optimal dose based on uric acid levels and tumor burden, dosing in obese patients and maximum dose.
-
tumor lysis syndrome pathophysiology definition and alternative treatment approaches
Clinical advances in hematology & oncology, 2005Co-Authors: Del Toro G, Erin Morris, Mitchell S CairoAbstract:Tumor lysis syndrome (TLS), a life threatening metabolic syndrome seen in malignancies with high tumor burden, is reviewed in this article. The new Cairo and Bishop classification system is discussed as well as the clinical management of this syndrome. Special emphasis is placed on the use of a relatively new agent, Rasburicase, as an alternative to allopurinol in the management of TLS-associated hyperuricemia.
F. Bonnete - One of the best experts on this subject based on the ideXlab platform.
-
Urate Oxidase Purification by Salting-in Crystallization : Towards an Alternative to Chromatography
PLoS ONE, 2011Co-Authors: Marion Giffard, N. Ferte, B. Castro, F. Ragot, M. El Hajji, F. BonneteAbstract:Background: Rasburicase (FasturtecH or ElitekH, Sanofi-Aventis), the recombinant form of urate oxidase from Aspergillus flavus, is a therapeutic enzyme used to prevent or decrease the high levels of uric acid in blood that can occur as a result of chemotherapy. It is produced by Sanofi-Aventis and currently purified via several standard steps of chromatography. This work explores the feasibility of replacing one or more chromatography steps in the downstream process by a crystallization step. It compares the efficacy of two crystallization techniques that have proven successful on pure urate oxidase, testing them on impure urate oxidase solutions.
-
Salting-In Effects on Urate Oxidase Crystal Design
Crystal Growth and Design, 2008Co-Authors: Marion Giffard, B. Castro, N. Ferte, Nathalie Colloc'h, F. BonneteAbstract:In this paper, solubility and interactions in solution of the recombinant urate oxidase from Aspergillus flavus, Rasburicase, are studied both in the absence and in the presence of salt at a pH close to the pI. An intense salting-in effect is demonstrated first by an increased solubility when various salts are added. Thus, merely adding salt does not induce Rasburicase crystallization. Second virial coefficient measurements also confirm this effect by exhibiting repulsive interactions over a large range of salt concentrations. Therefore, the salting-in effect enables the stabilization of Rasburicase solution at high concentrations. Moreover, it enables crystals of improved size and habit to be grown when polymer is added to a solution of Rasburicase concentrated with salt, or when salt is removed from it. We also show, with the example of high pressure macromolecular crystallography, that salt enables the stabilization of the desired polymorph under the highly concentrated polyethylene glycol conditions required by this technique.
-
A preliminary neutron diffraction study of Rasburicase, a recombinant urate oxidase enzyme, complexed with 8-azaxanthin
Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 2006Co-Authors: M. Budayova-spano, F. Bonnete, N. Ferte, F. Meilleur, M. Blakeley, B. CastroAbstract:Crystallization and preliminary neutron diffraction measurements of Rasburicase, a recombinant urate oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1 angstrom resolution using the LADI instrument from a crystal (grown in D2O) with volume 1.8 mm(3). The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high- resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, urate oxidase has one of the largest primitive unit- cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106 angstrom) and molecular weights (135 kDa for the homotetramer) so far successfully studied with neutrons.
Bertrand Coiffier - One of the best experts on this subject based on the ideXlab platform.
-
recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome tls in adults and children with malignant diseases an expert tls panel consensus
British Journal of Haematology, 2010Co-Authors: Mitchell S Cairo, Bertrand Coiffier, Alfred Reiter, Anas YounesAbstract:Tumour lysis syndrome (TLS) is a life-threatening oncological emergency characterized by metabolic abnormalities including hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. These metabolic complications predispose the cancer patient to clinical toxicities including renal insufficiency, cardiac arrhythmias, seizures, neurological complications and potentially sudden death. With the increased availability of newer therapeutic targeted agents, such as Rasburicase (recombinant urate oxidase), there are no published guidelines on the risk classification of TLS for individual patients at risk of developing this syndrome. We convened an international TLS expert consensus panel to develop guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. Risk factors included biological evidence of laboratory TLS (LTLS), proliferation, bulk and stage of malignant tumour and renal impairment and/or involvement at the time of TLS diagnosis. An international TLS consensus expert panel of paediatric and adult oncologists, experts in TLS pathophysiology and experts in TLS prophylaxis and management, developed a final model of low, intermediate and high risk TLS classification and associated TLS prophylaxis recommendations.
-
an integrated clinical approach for the identification prevention and treatment of tumor lysis syndrome
Cancer Treatment Reviews, 2010Co-Authors: Tariq I Mughal, Ahsan A Ejaz, John R Foringer, Bertrand CoiffierAbstract:Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic disorder that occurs when tumor cells undergo rapid decomposition spontaneously or in response to cytoreductive therapy. Delayed recognition of the metabolic imbalances caused by the massive release of tumor cell contents may result in clinical complications such as acute kidney injury, seizures, and cardiac arrhythmias. Prevention, the key principle in TLS management, relies on the identification of patients at risk for developing TLS during chemotherapy or because of disease progression. TLS-related risk factors pertain to tumor type (particularly hematologic malignancies), specific tumor characteristics (e.g. bulky tumor, high cellular proliferation rate, sensitivity to cytoreductive therapy), and other host-related factors. A comprehensive grading system proposed by Cairo and Bishop classifies TLS syndromes into laboratory or clinical TLS, thus facilitating TLS prevention and management. The mainstays of TLS management include monitoring of electrolyte abnormalities, vigorous hydration, prophylactic antihyperuricemic therapy with allopurinol, and Rasburicase treatment of patients at high TLS risk or with established hyperuricemia. Urine alkalinization and use of diuretics remain controversial clinical practices. In this review, we describe the incidence of, risk factors for, and diagnostic characteristics of TLS and summarize strategies for the prevention and management of TLS-associated metabolic abnormalities, particularly hyperuricemia. We specifically highlight recently published TLS management guidelines, which focus on the prevention of TLS and hyperuricemia based on a patient's level of risk, and the important role of nephrologists in the prevention and treatment of one of the most serious complications of TLS, acute kidney injury.
-
guidelines for the management of pediatric and adult tumor lysis syndrome an evidence based review
Journal of Clinical Oncology, 2008Co-Authors: Bertrand Coiffier, Ching-hon Pui, Anas Younes, Arnold J Altman, Mitchell S CairoAbstract:Purpose Tumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS. Methods A panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used. Results New guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic Rasburicase in high-risk patients, hydration plus allopurinol or Rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involve...
-
efficacy and safety of Rasburicase recombinant urate oxidase for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non hodgkin s lymphoma results of the graal1 groupe d etude des lymphomes de l adulte trial on
Journal of Clinical Oncology, 2003Co-Authors: Bertrand Coiffier, Nicolas Mounier, Serge Bologna, Christophe Ferme, Herve Tilly, Anne Sonet, Bernard Christian, Olivier Casasnovas, Eric Jourdan, Karim BelhadjAbstract:Purpose: Hyperuricemia and tumor lysis syndrome are well-known complications during induction treatment of aggressive non-Hodgkin’s lymphomas (NHLs). Usual prophylaxis and treatment of hyperuricemia consist of hydration, alkalinization, and administration of allopurinol. This study was designed to evaluate the efficacy and the safety of Rasburicase (recombinant urate oxidase) in adult patients with aggressive NHL during their first cycle of chemotherapy. Patients and Methods: A total of 100 patients from Groupe d’Etude des Lymphomes de l’Adulte centers, with diffuse large B-cell lymphoma (n = 79); anaplastic large-cell lymphoma (n = 6); peripheral T-cell lymphoma (n = 8); transformation of indolent lymphoma (n = 5); Burkitt’s lymphoma (n = 1); and lymphoblastic lymphoma (n = 1) were enrolled from May 2001 to June 2002. Before chemotherapy, 66% of patients had elevated lactate dehydrogenase (LDH), including 28% with LDH above 1,000 U/mL. Eleven percent of patients were hyperuricemic (uric acid [UA] > 450 m...
B. Castro - One of the best experts on this subject based on the ideXlab platform.
-
Urate Oxidase Purification by Salting-in Crystallization : Towards an Alternative to Chromatography
PLoS ONE, 2011Co-Authors: Marion Giffard, N. Ferte, B. Castro, F. Ragot, M. El Hajji, F. BonneteAbstract:Background: Rasburicase (FasturtecH or ElitekH, Sanofi-Aventis), the recombinant form of urate oxidase from Aspergillus flavus, is a therapeutic enzyme used to prevent or decrease the high levels of uric acid in blood that can occur as a result of chemotherapy. It is produced by Sanofi-Aventis and currently purified via several standard steps of chromatography. This work explores the feasibility of replacing one or more chromatography steps in the downstream process by a crystallization step. It compares the efficacy of two crystallization techniques that have proven successful on pure urate oxidase, testing them on impure urate oxidase solutions.
-
Salting-In Effects on Urate Oxidase Crystal Design
Crystal Growth and Design, 2008Co-Authors: Marion Giffard, B. Castro, N. Ferte, Nathalie Colloc'h, F. BonneteAbstract:In this paper, solubility and interactions in solution of the recombinant urate oxidase from Aspergillus flavus, Rasburicase, are studied both in the absence and in the presence of salt at a pH close to the pI. An intense salting-in effect is demonstrated first by an increased solubility when various salts are added. Thus, merely adding salt does not induce Rasburicase crystallization. Second virial coefficient measurements also confirm this effect by exhibiting repulsive interactions over a large range of salt concentrations. Therefore, the salting-in effect enables the stabilization of Rasburicase solution at high concentrations. Moreover, it enables crystals of improved size and habit to be grown when polymer is added to a solution of Rasburicase concentrated with salt, or when salt is removed from it. We also show, with the example of high pressure macromolecular crystallography, that salt enables the stabilization of the desired polymorph under the highly concentrated polyethylene glycol conditions required by this technique.
-
A preliminary neutron diffraction study of Rasburicase, a recombinant urate oxidase enzyme, complexed with 8-azaxanthin
Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 2006Co-Authors: M. Budayova-spano, F. Bonnete, N. Ferte, F. Meilleur, M. Blakeley, B. CastroAbstract:Crystallization and preliminary neutron diffraction measurements of Rasburicase, a recombinant urate oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1 angstrom resolution using the LADI instrument from a crystal (grown in D2O) with volume 1.8 mm(3). The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high- resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, urate oxidase has one of the largest primitive unit- cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106 angstrom) and molecular weights (135 kDa for the homotetramer) so far successfully studied with neutrons.
Ruemu Birhiray - One of the best experts on this subject based on the ideXlab platform.
-
i v ascorbic acid for treatment of apparent Rasburicase induced methemoglobinemia in a patient with acute kidney injury and assumed glucose 6 phosphate dehydrogenase deficiency
American Journal of Health-system Pharmacy, 2016Co-Authors: David J Reeves, Lindsay Saum, Ruemu BirhirayAbstract:Purpose A case of apparent Rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported. Summary A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. Laboratory test results revealed sustained hyperuricemia, which was believed to be due in part to tumor lysis, and a single dose of Rasburicase 6 mg i.v. was administered. Subsequently, the patient experienced a decrease in oxygen saturation. Methemoglobinemia was suspected, and the patient’s methemoglobin fraction was found to be 14.5%. The patient developed worsening shortness of breath and a drop in hemoglobin concentration, consistent with methemoglobinemia and hemolysis. Ascorbic acid 5 g i.v. every 6 hours was initiated for a total of six doses. Because the patient was assumed to have G6PD deficiency, which was later confirmed, methylene blue was avoided. Within 24 hours, the patient’s oxygen saturation values and symptoms improved. Conclusion A patient with apparent Rasburicase-induced methemoglobinemia and acute kidney injury was treated with i.v. ascorbic acid (5 g every six hours for six doses) because of the possibility, later proved, that he had G6PD deficiency. The methemoglobinemia resolved without worsening of renal function.
