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asparaginase allergy

Jiabao Liang, Pengcheng Shi, Xutao Guo, Jie Li, Lingli He, Yan Wang, Qi Wei, Fen Huang, Zhiping Fan, Bing Xu
Data from clinical trials suggest that polyethylene glycol-conjugated asparaginase (PEG asparaginase) should be recommended as a replacement for Escherichia coli (E. coli) asparaginase in the treatment of pediatric acute lymphoblastic leukemia (ALL) due to its prolonged effect, similar safety profile and convenience. The present study investigated the efficacy and safety of PEG asparaginase in adolescents and adults with newly diagnosed ALL. The clinical data of 122 patients, ≥14 years old with de novo ALL, who received either PEG asparaginase or E...
January 2018: Oncology Letters
Robin Q H Kloos, Carin A Uyl-de Groot, Raphaële R L van Litsenburg, Gertjan J L Kaspers, Rob Pieters, Inge M van der Sluis
BACKGROUND: Therapeutic drug monitoring (TDM) of asparaginase is necessary to respond to variability in asparaginase activity levels, detect silent inactivation, and distinguish between real allergies and allergic-like reactions with and without asparaginase neutralization, respectively. In this study, the costs of an individualized and fixed asparaginase dosing schedule were compared. PROCEDURE: Patients, treated according to the Dutch Childhood Oncology Group ALL-11 protocol (individualized PEGasparaginase treatment, starting dose: 1,500 IU/m2 ) or ALL-10 protocol (native Escherichia coli asparaginase followed by 2,500 IU/m2 PEGasparaginase), were included...
December 2017: Pediatric Blood & Cancer
Veerle Mondelaers, Stefan Suciu, Barbara De Moerloose, Alina Ferster, Françoise Mazingue, Geneviève Plat, Karima Yakouben, Anne Uyttebroeck, Patrick Lutz, Vitor Costa, Nicolas Sirvent, Emmanuel Plouvier, Martine Munzer, Maryline Poirée, Odile Minckes, Frédéric Millot, Dominique Plantaz, Philip Maes, Claire Hoyoux, Hélène Cavé, Pierre Rohrlich, Yves Bertrand, Yves Benoit
Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of non-very high-risk patients by comparing prolonged (long-asparaginase) versus standard (short-asparaginase) native E. coli asparaginase treatment in a randomized part of the phase III 58951 trial of the European Organization for Research and Treatment of Cancer Children's Leukemia Group. The main endpoint was disease-free survival...
October 2017: Haematologica
Rachid Abaji, Vincent Gagné, Chang Jiang Xu, Jean-François Spinella, Francesco Ceppi, Caroline Laverdière, Jean-Marie Leclerc, Stephen E Sallan, Donna Neuberg, Jeffery L Kutok, Lewis B Silverman, Daniel Sinnett, Maja Krajinovic
Allergy, pancreatitis and thrombosis are common side-effects of childhood acute lymphoblastic leukemia (ALL) treatment that are associated with the use of asparaginase (ASNase), a key component in most ALL treatment protocols. Starting with predicted functional germline variants obtained through whole-exome sequencing (WES) data of the Quebec childhood ALL cohort we performed exome-wide association studies with ASNase-related toxicities. A subset of top-ranking variants was further confirmed by genotyping (N=302) followed by validation in an independent replication group (N=282); except for thrombosis which was not available for that dataset...
July 4, 2017: Oncotarget
Lisa Persson, Arja Harila-Saari, Ida Hed Myrberg, Mats Heyman, Anna Nilsson, Susanna Ranta
BACKGROUND: Asparaginase (ASP) is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). It is also known for its ability to cause side effects, such as allergy and pancreatitis, as well as lipid and coagulation disturbances. The most important laboratory abnormalities are hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is usually considered to be transient and benign in children with ALL, whereas low AT activity predisposes to thrombosis. Studies on the incidence and significance of HTG in children with ALL are scarce, and their findings have not always been congruent...
October 2017: Pediatric Blood & Cancer
Chitose Ogawa, Fumi Taguchi, Hiroaki Goto, Katsuyoshi Koh, Daisuke Tomizawa, Akira Ohara, Atsushi Manabe
BACKGROUND: A phase I/II study of Erwinia asparaginase in Japanese children and young adults with acute lymphoblastic leukemia (ALL) was performed to investigate its activity and toxicity. PROCEDURE: Eligible patients were in remission and had developed allergy to Escherichia coli asparaginase. Erwina asparaginase was intramuscularly administrated on days 2, 5, 7, 9, 11, and 13. To measure the plasma l-asparagine concentration (PAC), amino acids were derivatized with N(α) -(5-fluoro-2,4-dinitrophenyl)-l-leucinamide...
September 2017: Pediatric Blood & Cancer
S E Karol, E Larsen, C Cheng, X Cao, W Yang, L B Ramsey, C A Fernandez, J R McCorkle, S W Paugh, R J Autry, E Lopez-Lopez, B Diouf, S Jeha, C-H Pui, E A Raetz, N J Winick, W L Carroll, S P Hunger, M L Loh, M Devidas, W E Evans, J J Yang, M V Relling
The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single-nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort...
June 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Wen-Jian Liu, Hua Wang, Wei-da Wang, Meng-Yuan Zhu, Cheng-Cheng Liu, Jing-Hua Wang, Yue Lu
Acute lymphoblastic leukemia (ALL) is a heterogeneous disease, and the long-term survival varies with different ages. We performed a retrospective analysis of 122 newly diagnosed adults with standard-risk ALL treated with Escherichia coli asparaginase (E. coli-asparaginase, n = 50) and polyethylene glycol-conjugated asparaginase (PEG-asparaginase, n = 72). No treatment-related mortality (TRM) occurred in the E. coli-asparaginase group, and 3 TRM events occurred in the PEG-asparaginase group without relation to asparaginase...
December 21, 2016: Scientific Reports
Jose A Cornejo-Garcia, Abderrahim Oussalah, Miguel Blanca, Rosa-Maria Gueant-Rodriguez, Cristobalina Mayorga, Julie Waton, Annick Barbaud, Francesco Gaeta, Antonino Romano, Jean-Louis Gueant
Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far...
2016: Current Pharmaceutical Design
Robin Q H Kloos, Rob Pieters, Gabriele Escherich, Inge M van der Sluis
BACKGROUND: Asparaginase is an important component of pediatric acute lymphoblastic leukemia (ALL) therapy. Unfortunately, this treatment is hampered by hypersensitivity reactions. In general, allergies - regardless of severity - cause complete inactivation of the drug. However, we report atypical allergic reactions without inactivation of asparaginase, here called allergic-like reactions. PROCEDURE: Patients with an allergic-like reaction, who were treated according to the Dutch Childhood Oncology Group ALL-11 or the CoALL 08-09 protocol, were described...
November 2016: Pediatric Blood & Cancer
Yan Xu, Jin Wang, Nan Yang, Ju Bai, Peng-Yu Zhang, Liu-Fang Gu, Bo Lei, Jie Liu, Fang-Xia Wang, Bing-Qiao Huang, Wang-Gang Zhang, Ai-Li He, Xing-Mei Cao, Yin-Xia Chen, Xiao-Rong Ma
OBJECTIVE: To explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients. METHODS: A total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control...
April 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Inge M van der Sluis, Lynda M Vrooman, Rob Pieters, Andre Baruchel, Gabriele Escherich, Nicholas Goulden, Veerle Mondelaers, Jose Sanchez de Toledo, Carmelo Rizzari, Lewis B Silverman, James A Whitlock
L-asparaginase is an integral component of therapy for acute lymphoblastic leukemia. However, asparaginase-related complications, including the development of hypersensitivity reactions, can limit its use in individual patients. Of considerable concern in the setting of clinical allergy is the development of neutralizing antibodies and associated asparaginase inactivity. Also problematic in the use of asparaginase is the potential for the development of silent inactivation, with the formation of neutralizing antibodies and reduced asparaginase activity in the absence of a clinically evident allergic reaction...
March 2016: Haematologica
Andrew E Place, Kristen E Stevenson, Lynda M Vrooman, Marian H Harris, Sarah K Hunt, Jane E O'Brien, Jeffrey G Supko, Barbara L Asselin, Uma H Athale, Luis A Clavell, Peter D Cole, Kara M Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A Schorin, Jennifer J G Welch, Steven E Lipshultz, Jeffery L Kutok, Traci M Blonquist, Donna S Neuberg, Stephen E Sallan, Lewis B Silverman
BACKGROUND: l-asparaginase is a universal component of treatment for childhood acute lymphoblastic leukaemia, and is usually administered intramuscularly. Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than the native Escherichia coli (E coli) preparation, and can be more feasibly administered intravenously. The aim of the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05-001 (DFCI 05-001) was to compare the relative toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E colil-asparaginase in children with newly diagnosed acute lymphoblastic leukaemia...
December 2015: Lancet Oncology
Lynda M Vrooman, Ivan I Kirov, ZoAnn E Dreyer, Michael Kelly, Nobuko Hijiya, Patrick Brown, Richard A Drachtman, Yoav H Messinger, A Kim Ritchey, Gregory A Hale, Kelly Maloney, Yuan Lu, Paul V Plourde, Lewis B Silverman
BACKGROUND: Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase...
February 2016: Pediatric Blood & Cancer
Christian A Fernandez, Colton Smith, Wenjian Yang, Charles G Mullighan, Chunxu Qu, Eric Larsen, W Paul Bowman, Chengcheng Liu, Laura B Ramsey, Tamara Chang, Seth E Karol, Mignon L Loh, Elizabeth A Raetz, Naomi J Winick, Stephen P Hunger, William L Carroll, Sima Jeha, Ching-Hon Pui, William E Evans, Meenakshi Devidas, Mary V Relling
Asparaginase is used to treat acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions can lead to suboptimal asparaginase exposure. Our objective was to use a genome-wide approach to identify loci associated with asparaginase hypersensitivity in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols Total XIIIA (n = 154), Total XV (n = 498), and Total XVI (n = 271), or Children's Oncology Group protocols POG 9906 (n = 222) and AALL0232 (n = 2163). Germline DNA was genotyped using the Affymetrix 500K, Affymetrix 6...
July 2, 2015: Blood
L N Ramya, Krishna Kanth Pulicherla
Protein therapeutics, particularly of heterologous origin are shown to elicit immunogenic responses which result in adverse allergic reactions in spite of their promising clinical benefit. L-Asparaginase is one such well known chemotherapeutic agent that has enhanced the survival rates to 90 % in the treatment of acute lymphoblastic leukaemia for past 30 years. But the use of this enzyme is accompanied by hypersensitive reactions ranging from allergy to anaphylactic shock which have a drastic influence in treatment outcomes...
September 2015: Pathology Oncology Research: POR
Vladan Rajić, Maruša Debeljak, Katja Goričar, Janez Jazbec
l-asparaginase is an effective antineoplastic agent used in chemotherapy of acute lymphoblastic leukemia. The drug effect may be compromised by an elicited immune response, resulting in the production of anti-asparaginase antibodies causing an anaphylactic reaction or silent inactivation of the enzyme. To elucidate possible genetic predisposition for inter-individual differences in asparaginase hypersensitivity, we studied single nucleotide polymorphisms (SNPs) in the GRIA1 gene in 146 pediatric patients treated with l-asparaginase...
2015: Leukemia & Lymphoma
Christian A Fernandez, Colton Smith, Seth E Karol, Laura B Ramsey, Chengcheng Liu, Ching-Hon Pui, Sima Jeha, William E Evans, Fred D Finkelman, Mary V Relling
A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10(-13)) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10(-3)) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies...
March 2015: Journal of Pharmacology and Experimental Therapeutics
Louise Tram Henriksen, Arja Harila-Saari, Ellen Ruud, Jonas Abrahamsson, Kaie Pruunsild, Goda Vaitkeviciene, Ólafur Gísli Jónsson, Kjeld Schmiegelow, Mats Heyman, Henrik Schrøder, Birgitte Klug Albertsen
BACKGROUND: L-Asparaginase is an effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL). The use of L-asparaginase may be limited by serious adverse events of which allergy is the most frequent. The objective of this study was to describe the clinical aspects of PEG-asparaginase allergy in children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol. PROCEDURE: Children (1-17 years) enrolled in the NOPHO ALL2008 protocol between July 2008 and August 2011, who developed PEG-asparaginase allergy were identified through the NOPHO ALL2008 toxicity registry...
March 2015: Pediatric Blood & Cancer
Archie Bleyer, Barbara L Asselin, Susannah E Koontz, Stephen P Hunger
Asparaginase, an enzyme used to treat acute lymphoblastic leukemia and related forms of nonHodgkin lymphoma, depletes asparagine, which leads to lymphoblast cell death. Unlike most chemotherapeutic agents, asparaginase is a foreign protein that can result in clinical allergy and/or silent hypersensitivity with production of neutralizing antibodies that inactivate asparaginase. In North America, asparaginase activity levels can now be obtained via a commercially available assay, for therapeutic drug monitoring and investigation of potential allergic reactions...
June 2015: Pediatric Blood & Cancer
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