Desensitization protocol should not be used in acute lymphoblastic leukemia patients with silent inactivation of PEGasparaginase

Tong, Wing H.; Pieters, Rob; Tissing, Wim J. E.; Sluis, Inge M. van der

doi:10.3324/haematol.2013.099663

Cited by 18 publications

(15 citation statements)

References 11 publications

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“…[7,14,42,77] As patients with subclinical hypersensitivity exhibit no apparent symptoms, treatment with the same asparaginase formulation is often continued, possibly with insufficient asparaginase activity and no therapeutic benefit. [42,79] …”

Section: Asparaginase Pharmacokineticsmentioning

confidence: 99%

“…If subclinical hypersensitivity is identified, it is recommended that patients be switched to the alternate formulation asparaginase Erwinia chrysanthemi. [7,42,79,99] Once a patient is switched, TDM can also be used to assess asparaginase activity related to the shorter half-life of asparaginase Erwinia chrysanthemi to determine whether patients are obtaining satisfactory asparagine depletion over the 72-h weekend with IV versus IM administration.…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

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Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Burke

Rheingold

2016

Leukemia & Lymphoma

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Asparaginase is a key component of therapy for acute lymphoblastic leukemia (ALL). Traditionally, asparaginase was administered intramuscularly but is now commonly given intravenously. Although intravenous administration is less painful, it can be challenging to differentiate hypersensitivity versus infusion-related reactions. The ability to distinguish between asparaginase-mediated reactions is critical to ensure optimal asparaginase treatment. In this paper, we will review the differences in pharmacokinetics and toxicities, when asparaginase is administered intravenously versus intramuscularly in pediatric patients with ALL. Differences between antibody-mediated hypersensitivity events and nonantibody-mediated infusion reactions will be addressed to assist practitioners in distinguishing between these clinically similar asparaginase-associated toxicities.ARTICLE HISTORY

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Section: Asparaginase Pharmacokineticsmentioning

confidence: 99%

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Burke

Rheingold

2016

Leukemia & Lymphoma

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“…Ideally, patients who develop grade ≥2 hypersensitivity to PEG asparaginase should be switched to asparaginase E. chrysanthemi as soon as symptoms resolve to avoid any possible gaps in asparagine depletion [29]. Successful rechallenge of the same formulation following hypersensitivity has been reported with various desensitization protocols; however, these measures are usually reserved for cases when a sparaginase E. chrysanthemi is unavailable [87,88].…”

Section: • • Clinical Hypersensitivity Reactionsmentioning

confidence: 99%

Immunology of Infusion Reactions in The Treatment of Patients with Acute Lymphoblastic Leukemia

Asselin

2016

Future Oncol.

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Infusion reactions are potentially dose-limiting adverse events associated with intravenous administration of several common agents used to treat patients with acute lymphoblastic leukemia. True clinical hypersensitivity reactions are antibody-mediated and can occur only after repeated exposure to an antigen. Conversely, anaphylactoid infusion reactions are nonantibody-mediated and often occur on the initial exposure to a drug. Cytokine-release syndrome comprises a subset of nonantibody-mediated infusion reactions associated with the use of monoclonal antibodies and immune therapies. Clinical symptoms of hypersensitivity reactions and nonantibody-mediated infusion reactions heavily overlap and can be difficult to distinguish in practice. Regardless of the underlying mechanism, any infusion reaction can negatively affect treatment efficacy and patient safety. These events require prompt response, and potentially, modification of subsequent therapy.

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“…Atualmente, existem três formas da enzima terapeuticamente utilizadas, todas obtidas a partir de cepas bacterianas. Porém, embora este citostático tenha sido uma das maiores contribuições para o tratamento da LLA nos últimos anos, seu uso é ainda limitado devido aos importantes efeitos colaterais (GUILLEME et al, 2013;TONG et al, 2014;NARTA;KANWAR;AZMI, 2007), além de que sua formulação e dosagem ideais continuam sendo muito discutidas (PIETERS et al, 2011 (GRAHAM, 2003;FERNANDEZ et al, 2013;GUILLEME et al, 2013 (BROMME, 1963a(BROMME, , 1963b A L-Asparaginase é um bioproduto muito importante pois possui um amplo espectro de atividade antitumoral. O seu mecanismo antileucêmico conta com a conversão da L-Asparagina em aspartato a partir da hidrólise do aminoácido (MOOLA et al, 1994;RICHARDS;KILBERG, 2006 RYTTING, 2014;RIZZARI et al, 2013).…”

Section: Leucemia Linfóide Agudaunclassified

“…Kurtzberg e colaboradores (2011) citam ainda que, logo após a administração da enzima derivada de E. coli, a incidência de reações de hipersensibilidade fica em torno de 4% durante a fase de indução do tratamento, porém, pode chegar a 80% naqueles pacientes que forem expostos a doses adicionais (KURTZBERG et al, 2011). As reações de hipersensibilidade são acompanhadas da produção de anticorpos anti-LAsparaginase, principal causa de resistência ao medicamento, essa que pode ser sintomática, com sinais de hipersensibilidade clínica, ou assintomática, sem quaisquer sinais (PANOSYAN et al, 2004;PIETERS et al, 2011;TONG et al, 2014;RIZZARI et al, 2013). Ambas resultam na redução da atividade enzimática e, consequentemente, a efetiva depleção de L-Asparagina no plasma não irá ocorrer (AVRAMIS et al, 2002) e, em alguns casos, a atividade enzimática pode ser indetectável (PANOSYAN et al, 2004;KAWEDIA;RYTTING, 2014 (NARAZAKI et al, 2012).…”

Section: Leucemia Linfóide Agudaunclassified

Avaliação da produção de L- Asparaginase por fungos isolados do bioma Cerrado

Almeida¹

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A Deus, por mais essa etapa vencida em minha vida.A Professora Dra. Pérola de Oliveira Magalhães Dias Batista, pela oportunidade, confiança e amizade. Seus estímulos, apoio e questionamentos foram fundamentais para a conclusão desse trabalho. Muito obrigada.Ao meu maior incentivador, companheiro de todas as horas, meu amor Bruno.Obrigada pelo carinho, compreensão, apoio e paciência neste período e em todos os momentos da minha vida. Amo muito você.Aos meus pais, Renato e Magda, e ao meu irmão, Mateus, que, mesmo distantes, incentivam e compartilham os grandes momentos da minha vida. Sem vocês, nada disso seria possível.A toda minha família que sempre torceu muito pelas minhas conquistas, especialmente a minha tão amada avó, Maria, que sempre me protege e abençoa em suas orações.As professoras Dra. Maria de Fátima Borin e Dra. Eliete Neves da Silva Guerra, por terem aceitado o convite e participarem como membros da banca de avaliação deste trabalho. Meus sinceros agradecimentos pela atenção dispensada. Além disso, meu muito obrigada pelas palavras de apoio e incentivo nos momentos mais difíceis, serei eternamente grata por tudo.À CAPES pelo suporte financeiro concedido.A todas as pessoas que direta ou indiretamente contribuíram para o desenvolvimento e conclusão deste trabalho, meu muito obrigada. Asparaginase strain producer, were used. Subsequently, 42 fungal strains from the brazilian savanna were isolated and a screening to assess the ability of the same for the production of L-Asparaginase was performed through the halo test. Out of the 42 isolated stains, 22 species showed red halo, which may indicate the production of LAsparaginase. These 22 species were cultivated in the liquid medium under controlled agitation and temperature and only 10 were positive for enzyme production. Then, the top 3 producing strains were grown in different culture conditions to improve the production of L-Asparaginase. Regarding the carbon sources, glucose utilization was essential for enzyme production. L-Proline seems to be the most effective source of nitrogen for producing L-Asparaginase. In addition, were found different optimum pH values of the different fungal strains cultivation.

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Desensitization protocol should not be used in acute lymphoblastic leukemia patients with silent inactivation of PEGasparaginase

Cited by 18 publications

References 11 publications

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Immunology of Infusion Reactions in The Treatment of Patients with Acute Lymphoblastic Leukemia

Avaliação da produção de L- Asparaginase por fungos isolados do bioma Cerrado

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