Carboplatin-allergic patients undergoing desensitization: prevalence and impact of the BRCA 1/2 mutation

Galvão, Violeta Régnier; Phillips, E.; Giavina‐Bianchi, Pedro; Castells, Mariana

doi:10.1016/j.jaip.2016.08.012

Cited by 26 publications

(16 citation statements)

References 9 publications

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“…For female patients with ovarian cancer presenting with BRCA1 and BRCA2 mutations, carboplatin allergy occurs early and with fewer exposures. 2,58…”

Section: Basophil Activation Testmentioning

confidence: 99%

“…Mastocytosis and clonal mast cell disorders can present as anaphylaxis with or without known triggers, 66 and the incidence of anaphylaxis is increased in male patients with systemic mastocytosis and increased IgE levels. 53 Patients presenting with recurrent hypotension with cardiovascular collapse in the absence of urticaria or angioedema are at high risk for clonal mast cell disorders, 58,67 and the KIT D816V mutation should be investigated along with tryptase levels. Patients with monoclonal mast cell activation syndrome and early stages of systemic mastocytosis can have normal tryptase levels.…”

Section: Mast Cell Clonal Disorders and Anaphylaxismentioning

confidence: 99%

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Diagnosis and management of anaphylaxis in precision medicine

Castells

2017

Journal of Allergy and Clinical Immunology

216

170

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Anaphylaxis is the most severe and frightening of the allergic reactions, placing patients at high risk and demanding prompt recognition and immediate management by health care providers. Yet because its symptoms imitate those of other diseases, such as asthma and urticaria, current data suggest that its diagnosis is often missed, with underuse of tryptase measurement; its treatment is delayed, with little use of epinephrine; and its underlying cause or causes are poorly investigated. Deaths from anaphylaxis are difficult to investigate because of miscoding. Surprisingly, patients treated with new and powerful chemotherapy agents and humanized mAbs present with nonclassical symptoms of anaphylaxis, and patients may present with unrecognized clonal mast cell disorders with KIT mutations may present as Hymenoptera-induced or idiopathic anaphylaxis. The goal of this review is to recognize the presentations of anaphylaxis with the description of its current phenotypes, to provide new insight and understanding of its mechanisms and causes through its endotypes, and to address its biomarkers for broad clinical use. Ultimately, the aim is to empower allergists and heath care providers with new tools that can help alleviate patients' symptoms, preventing and protecting them against anaphylaxis.

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“…For female patients with ovarian cancer presenting with BRCA1 and BRCA2 mutations, carboplatin allergy occurs early and with fewer exposures. 2,58…”

Section: Basophil Activation Testmentioning

confidence: 99%

Section: Mast Cell Clonal Disorders and Anaphylaxismentioning

confidence: 99%

Diagnosis and management of anaphylaxis in precision medicine

Castells

2017

Journal of Allergy and Clinical Immunology

216

170

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“…Phenotypes in drug allergy focus on symptoms and timing, classifying the reactions as immediate or delayed, depending on the time between treatment administration and the onset of symptoms. Endotypes, based on cellular and biological mediators as well as biomarkers, have become vital to elucidate the molecular pathways as well as to evaluate the risk for reaction during re-exposure to the culprit drug [ 1 , 9 , 10 , 11 , 12 ]. Genetic predisposition has been shown to play a role in the development of HSRs to anticonvulsants, sulfonamides, and abacavir among others.…”

Section: Drug Hypersensitivity Reactions: New Clinical Approach Thmentioning

confidence: 99%

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

Vecillas

Alenazy

Garcia-Neuer

et al. 2017

IJMS

113

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Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications.

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“…Allergic symptoms typically start at the second round of treatment, when the cancer recurs and after 1–2 exposures sensitized patients present with flushing and pruritus which can progress to shortness of breath with further exposure and can lead to anaphylaxis, with hypotension and cardiovascular collapse ( 2 , 4 , 7 , 33 , 45 ). Patients bearing BRCA 1 and 2 gene mutations have an increased risk for carboplatin reactions, which can occur with fewer exposures ( 46 , 47 ). Most reactions to platins occur during or shortly after the drug infusion and the phenotype is that of type I reaction.…”

Section: Drug Desensitizationmentioning

confidence: 99%

Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: The Role of Desensitizations

Castells

2017

Front. Immunol.

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Drug allergy is a rising problem in the twenty-first century which affects all populations and races, children, and adults, and for which the recognition, diagnosis, management, and treatment is still not well standardized. Classical and new chemotherapy drugs, monoclonal antibodies (MoAbs), and small molecules to treat cancer and chronic inflammatory diseases are aimed at improving quality of life and life expectancy of patients, but an increasing number of reactions including anaphylaxis precludes their use in targeted populations. Women are more affected by drug allergy and up to 27% of women with ovarian and breast cancer develop carboplatin allergy after multiple cycles of treatment. Carriers of BRCA genes develop drug allergy after fewer exposures and can present with severe reactions, including anaphylaxis. Atopic patients are at increased risk for chemotherapy and MoAbs drug allergy and the current patterns of treatment with recurrent and intermittent drug exposures may favor the development of drug allergies. To overcome drug allergy, desensitization has been developed, a novel approach which provides a unique opportunity to protect against anaphylaxis and to improve clinical outcomes. There is evidence that inhibitory mechanisms blocking IgE/antigen mast cell activation are active during desensitization, enhancing safety. Whether desensitization modulates drug allergic and anaphylactic responses facilitating tolerance is currently being investigated. This review provides insight into the current knowledge of drug allergy and anaphylaxis to cancer and chronic inflammatory diseases drugs, the mechanisms of drug desensitization and its applications to personalized medicine.

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Carboplatin-allergic patients undergoing desensitization: prevalence and impact of the BRCA 1/2 mutation

Cited by 26 publications

References 9 publications

Diagnosis and management of anaphylaxis in precision medicine

Diagnosis and management of anaphylaxis in precision medicine

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: The Role of Desensitizations

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