asparaginase IgE

BACKGROUND: Pegaspargase is a therapeutic enzyme that is utilized in treatment regimens targeting pediatric acute lymphoblastic leukemia. However, many patients experience hypersensitivity reactions, requiring discontinuation of the therapy. Historically, this necessitated switching to an alternative form of the drug, most commonly asparaginase Erwinia chrysanthemi; however, in recent years this was difficult due to drug shortages and eventually commercial discontinuation. We report here our experience performing pegaspargase desensitizations in patients with prior hypersensitivity reactions...

L-asparaginase is effective as part of the first line childhood acute lymphoblastic leukaemia (ALL) treatment regimen but suffers the risk of antibody production causing immune-mediated sequelae. This article aimed to describe the clinical implication of L-asparaginase hypersensitivity and review the types of antibodies and genetic polymorphisms contributing to it. Clinical or subclinical L-asparaginase hypersensitivity may lead to suboptimum therapeutic effect and jeopardise the clinical outcome in ALL children...

The family of nuclear factor of activated T cells (NFAT) transcription factors plays a critical role in mediating immune responses. Our previous clinical pharmacogenetic studies suggested that NFATC2 is associated with the risk of hypersensitivity reactions to the chemotherapeutic agent L-asparaginase (ASNase) that worsen outcomes during the treatment of pediatric acute lymphoblastic leukemia. We therefore hypothesized that the genetic inhibition of NFATC2 would protect against the development of anti-ASNase antibodies and ASNase hypersensitivity...

BACKGROUND: L-asparaginase (L-asp) remains one of the key components of acute lymphoblastic leukemia therapy. Immune reactions to the drug are associated with its diminished activity. The aim of the study was to determine the level of IgM, IgG and IgE-class anti-L-asp antibodies during the induction and reinduction phases of acute lymphoblastic leukemia therapy and their influence on L-asp activity. METHODS: The study group comprised 65 patients treated for acute lymphoblastic leukemia in one pediatric oncology center...

Asparaginase is an important drug for the treatment of leukemias. However, anti-asparaginase antibodies often develop, which can decrease asparaginase drug levels and increase the risk of relapse. The aim of this study is to identify the immunoglobulin isotypes and receptors responsible for asparaginase hypersensitivities. Mice immunized with asparaginase developed anti-asparaginase IgG1 and IgE antibodies, and challenging the sensitized mice with asparaginase induced severe hypersensitivity reactions. Flow cytometry analysis indicated that macrophages/monocytes, neutrophils, and basophils bind asparaginase ex vivo through FcγRIII...

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...

Escherichia coli -derived L-asparaginases have been used in the treatment of acute lymphoblastic leukemia (ALL), however, clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli -asparaginase, lead to inactivation of these preparations in most cases.Therefore, this study was aimed to investigate the cytotoxicity and antitumor effects ofa novel L-asparaginaseenzyme, isolated from Phaseolus vulgaris seeds (P-Asp) on the ALL cell line (Jurkat). The immunogenicity of the enzyme was also evaluated in-vivo and results were compared to commercially available enzymes of microbial sources...

Use of cytotoxic agents is associated with potential hypersensitivity reactions which are common with platinum compounds, L-asparaginase, taxanes, procarbazine and epipodophyllotoxins. Mechanisms underlying the reactions may involve IgE, non-allergic or a number of pathogenetically unclear events. Targeted therapies produce less collateral damage but demonstrate their own unique reactions. Cytopenias occur less often and mucocutaneous reactions to EGFR inhibitors, including papulopustular rash, are common. Fifteen currently approved mAbs provoke all four types of hypersensitivities including immune cytopenias, vasculitis, serum sickness and pulmonary events...

Immediate allergy to l-asparaginase (ASP) is a major obstacle in treating lymphoid malignancies. ASP-specific immunoglobulin G (ASP-IgG) has been used as a surrogate marker. Recently, the CD203c-basophil activation test (BAT) was found to be useful in diagnosing IgE-mediated allergies. We compared the diagnostic utility of the CD203c-BAT to that of ASP-IgG levels in determining ASP allergies in children. Eight ASP allergic reactions occurred over 75 ASP treatment courses. The sensitivity, specificity and area under the receiver operating characteristic curve of CD203c-BAT were similar to the ASP-IgG levels (0...

Drug hypersensitivity reactions (HSR) are adverse events resembling allergy which occur at therapeutic doses. Both anticancer chemotherapeutics and monoclonal antibodies have the potential for acute HSR. all infusion reactions involve the immune system; however, some (anaphylactic) are allergic in nature and usually are mediated by immunoglobulin E (IgE), whereas others (anaphylactoid) are not true allergic reactions and are not mediated by IgE. although HSR can be allergic or nonallergic, the clinical manifestations are the same and require prompt, accurate assessment and management to avoid severe adverse events, including fatality...

The number of drugs used for the treatment of different types of cancers is constantly increasing and actually exceeds 100 distinct chemical formulations. The use of most cytotoxic agents is associated with potential hypersensitivity reactions, and the constant increase of their administration has caused an increase in incidence of these adverse effects, thus becoming a relevant problem for clinicians. Hypersensitivity reactions are common with platinum compounds, L-asparaginase, taxanes, procarbazine, and epipodophyllotoxins, whereas they are unusual, but always possible, with the other chemotherapeutic drugs...

OBJECTIVES: To review clinical hypersensitivity reactions related to common cancer chemotherapy agents and to discuss potential management strategies. DATA SOURCES: PubMed searches were performed for articles published from 1970 to 2008 regarding hypersensitivity to cancer chemotherapy and related agents using the keywords hypersensitivity, allergy, chemotherapy, platinums, taxanes, asparaginase, epipodophyllotoxins, and procarbazine. Retrieved articles were surveyed for additional citations...

X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand (CD40L) gene with normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE. Liver disease may occur as a clinical manifestation in XHIGM. This complication appears to increase with age. We report an 18-year-old male patient who had recurrent episodes of acalculous cholecystitis (AC) and sclerosing cholangitis (SC). The diagnosis of XHIGM was confirmed by the finding of CD40L expression < 1% of normal and a tyrosine 169 asparaginase (t526a) mutation in exon 5 (the tumor necrosis factor domain) of the CD40L gene...

UNLABELLED: We analyzed the dynamics of changes in the immune system during maintenance treatment of acute lymphoblastic leukemia (ALL). The study was carried out on the group of 40 children aged 2-15 years (mean +/- 3.46), including 31 lower risk patients (Berlin-Frankfurt-Munich protocol--BFM) and 9 high risk patients (New York protocol--NY). Levels of IgA, IgG, IgM and IgE, and subsets of mononuclear cells using flow cytometry were evaluated in the study group every 1-3 months. During maintenance therapy we found markedly reduced leukocytosis, lymphocytosis, and mean values of IgA, IgM and IgG in comparison to healthy children...

OBJECTIVE: A pilot clinical study was conducted to evaluate the toxicity of a single dose of L-asparaginase loaded in red blood cells (RBCs). METHODS: Thirteen patients received a single dose of L-asparaginase in the range 30-200 i.u.kg-1. The enzyme was loaded in one autologous blood unit using a lysis-resealing process. A control population of 33 patients receiving L-asparaginase intravenously were tested in parallel. IgG, IgM and IgE class anti-L-asparaginase antibodies were detected using specific radioimmunoassays...

The covalent attachment of poly-DL-alanine peptides to lysyl residues on the surface of Erwinia carotovora L-asparaginase has produced a modified enzyme which is much less immunogenic in mice and demonstrates 100-fold longer plasma half-life in the rhesus monkey. Immunogenic responses towards both the immunoglobulin G (IgG) and immunoglobulin E (IgE) antibody subclasses were evaluated in C57BL x DBA/2 F1 mice exposed to 250 rads of whole-body irradiation 4 hr prior to immunization with 5-diazo-4-oxynorvaline-inactivated native and modified L-asparaginase in complete Freund's adjuvant...

No abstract text is available yet for this article.

The anti-tumor activity of L-asparaginase (EC. 3.5.1.1.) has been conclusively demonstrated. Its therapeutic application, however, has been hampered by its short clearance time in the circulation and high immunogenicity. In order to solve these problems, polyethylene glycol, a linear synthetic and non-immunogenic polymer, was introduced covalently into the amino groups in the enzyme molecule. Monomethoxypolyethylene glycol with molecular weight of 5000 was activated with cyanuric chloride to obtain activated PEGs [2, 4-bis (O-methoxypolyethyleneglycol)-6-chloro-s-triazine]...

No abstract text is available yet for this article.

No abstract text is available yet for this article.