Antibodies were absent in all but one patient with an allergiclike reaction while they were detected in all patients with a real allergy. Despite its indisputable indication, hypersensitivity reactions are common. Other hypersensitivity reactions can include angioedema, lip swelling, eye swelling. Throughout the united states, nurses assume frontline responsibility for the assessment of asparaginaserelated hypersensitivity reactions. L asparaginase is effective in the treatment of malignant diseases, but it has been associated with hypersensitivity reactions in 5% to 45% of the patients. Aug 30, 2017 asparaginase encapsulated in erythrocytes for patients with all and hypersensitivity to peg asparaginase the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. However, asparaginase induced hypersensitivity reactions can compromise its efficacy either by directly influencing the pharmacokinetics of asparaginase or by leading to a discontinuation of asparaginase treatment. Pegasparaginase may decrease, although not eliminate the risk for an hsr and reactions are often milder. Serious hypersensitivity reactions, including anaphylaxis, reported. We studied allergic reactions and serum antibodies to e. The incidence of hypersensitivity reactions to pegylated asparaginase in children with all.
Aug 21, 2014 the story with asparaginase is somewhat different. It is essential that nurses educate themselves on the signs and symptoms of asparaginase related hypersensitivity reactions. The alternative, pegylated asparaginase was developed for patients with allergic reactions to the native enzyme and is associated with allergic reactions to the pegylated moiety, 7 which exists in canned food and cosmetic products. Review of pharmacogenetics studies of lasparaginase. Anaphylaxis and serious hypersensitivity reactions can occur in patients receiving oncaspar. Erwinaze asparaginase erwinia chrysanthemi is indicated as a component of a multiagent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia all who have developed hypersensitivity to e. Rheingoldb adivision of pediatric oncology, medical college of wisconsin, milwaukee, wi, usa. The native asparaginase, used in the pediatric studies, 1 was recently removed from the market. Severe hsr of pegaspargase via iv or im route of administration necessitates substitution with antigenically distinct erwinia asparaginase. Patients receiving pegaspargase may experience hypersensitivity reactions including anaphylaxis, bronchospasm, hypotension, laryngeal oedema, local erythema or swelling, rash and urticaria and the risk of serious hypersensitivity reaction is particularly high in patients with known hypersensitivity to e.
Reactions to a single administration are rare, but since native l asparaginase is isolated from e. Hypersensitivity reactions to pegasparaginase are more common when patients have been previously exposed to native e. Asparaginase products may produce acute hypersensitivity reactions with hypotension, sweating, bronchospasm, and urticaria. Here, we report successful challenges using native escherichia coli asparaginase. Reactions can range from local reactions more common to anaphylactic reactions, including skin rash, erythema, swelling, urticaria, pruritus, arthralgia, bronchospasm, wheezing, laryngeal edema, hypotension, respiratory andor cardiovascular collapse and death.
How to manage asparaginase hypersensitivity in acute. Clinical hypersensitivity reactions against commercially available asparaginase have resulted in failure of asparaginase in treatment of all in more than 60% of cases. Toxicity, other than hypersensitivity reactions, may be more severe when the drug is administered daily rather than weekly. Thus, it is required to search for serologically different asparaginase from new organisms for the. Grade 1 or mild hypersensitivity reactions transient rash. Pharmacogenetics of asparaginase in acute lymphoblastic leukemia. Pegasparaginase hypersensitivity reactions developed during a median of 3 iv infusions range. Immune reactions in patients treated with asparaginase fall into two general categories. History of serious thrombosis with prior l asparaginase therapy history of serious hemorrhagic events with prior l asparaginase therapy 5 warnings and precautions 5. A murine model was developed that recapitulates key features of clinical hypersensitivity to escherichia coli asparaginase. Hypersensitivity reactions may necessitate the discontinuation of e. Asparaginase is an essential component of pediatric acute lymphoblastic leukemia all therapy. A promising enzyme for treatment of acute lymphoblastic leukiemia richa jain, k. Hypersensitivity reactions to asparaginase therapy can occur in 30% of children with acute lymphoblastic leukemia all, and silent inactivation with the formation of neutralizing antibodies and reduced asparaginase activity can occur in the absence of a clinically evident allergic reaction.
Clinical hypersensitivity reactions to elspar in studies were common ranging from 32. Antibodies may directly bind to the surface of the mast cell, thereby activating the mast cell 5. Subgroups of paediatric acute lymphoblastic leukaemia. In these studies, concomitant medications and dosing schedules varied. Tracking silent hypersensitivity reactions to asparaginase. Hypersensitivity reaction hsr rates with these agents are common, multifactorial, and treatmentaltering. It is effective in treating acute lymphoblastic leukemia all and other related.
Asparaginase is a key component of therapy for acute lymphoblastic leukemia all. Other hypersensitivity reactions can include angioedema, lip swelling, eye. Managing asparaginase hypersensitivity in pediatric and. Lasparaginase is effective in the treatment of malignant diseases, but it has been associated with hypersensitivity reactions in 5% to 45% of the patients. The other 35% had no prior hypersensitivity reaction to native asparaginase. Hypersensitivity reactions to lasparaginase do not impact. In those cases, discontinuation of treatment is usually needed and anti asparaginase antibody production may also attenuate asparaginase activity, compromising its antileukemic effect. Hypersensitivity rates in pediatric patients receiving.
Clinical hypersensitivity to escherichia coli asparaginase has been reported to range from 0% to 75%. Polyethyleneglycolated peg asparaginase pegasp is a crucial component of pediatric acute lymphoblastic leukemia therapy. Differentiating hypersensitivity versus infusionrelated. Reactions whose route of administration was iv were more severe than the im reactions, a statistically significant result. Silent hypersensitivity reactions to this microbial enzyme need to be monitored accurately during treatment to avoid adverse effects of the drug and its silent inactivation. Managing hypersensitivity to asparaginase in pediatrics. Because asparaginase is a large protein that is foreign to the human body, it is commonly associated with hypersensitivity reactions. History of serious hypersensitivity reactions to asparaginase erwinia chrysanthemi, including anaphylaxis. How to solve the problem of hypersensitivity to asparaginase. For pegasp, a metaanalysis showed a reduction in hypersensitivity reactions when administration occurs by the im route, in comparison to the iv route, in. Clinical characteristics of intravenous pegasparaginase. Nurses administering peg asparaginase play a critical role in the early identification and management of hypersensitivity reactions.
Toxicity, other than hypersensitivity reactions, may be more severe when the drug is administered. When intravenous iv infusion replaced intramuscular im injection as the standard route of administration, there were early reports suggested an increased hypersensitivity reactions hsrs rate with iv administration. However, hypersensitivity reactions hsrs to asp are major challenges in paediatric patients. Do not receive any kind of immunization or vaccination without your doctors approval while taking asparaginase. Additional research is needed to safely guide peg asparaginase monitoring, hypersensitivity reaction management, and patientfamily education. Asparaginase is an enzyme that is used as a medication and in food manufacturing. Hypersensitivity reactions to chemotherapeutic drugs have been documented for numerous cancer therapies. Consensus expert recommendations for identification and. Jan 02, 2020 options for patients after allergic reactions to pegaspargase include rechallenging with premedications, switching to erwinia asparaginase, or discontinuation of asparaginase therapy. Samples were sent after changing treatment to another drug because of hypersensitivity reactions in an additional 276 patients.
The prevalence of clinical hypersensitivity with asparaginase therapy depends on a number of factors including the type of asparaginase used, treatment intensity and history, concurrent corticosteroid use, and patient age and genetics. Hypersensitivity reactions to chemotherapeutic drugs. Guidelines on asparaginase hypersensitivity and silent. Subgroups of paediatric acute lymphoblastic leukaemia might.
Asparaginase encapsulated in erythrocytes for patients with. Hypersensitivity is an immunologic response 5 hypersensitivity reactions are mediated by the immune system 5. An antigen, such as asparaginase, may trigger an immune response, which results in the proliferation of antibodyproducing plasma cells 5. Almost all chemotherapeutic agents can cause an allergic reaction. We describe associations of allergic reactions and antiasparaginase. Asparaginase, pharmacogenomics, hypersensitivity reactions, pancreatitis, relapse, acute lymphoblastic leukemia, adverse drug reactions asparaginase and acute lymphoblastic leukemia l asparaginase asnase is a key component in leukemias and lymphomas treatment strategies and is universally incorporated into major childhood acute lymphoblastic. Hypersensitivity reactions associated with lasparaginase. Clinical hypersensitivity occurs frequently in post induction regimens when asparaginase has not been given for weeks or months, but reactions have been reported after the first dose.
Information on asparaginase hypersensitivity in this patient population is limited. Differentiating hypersensitivity versus infusionrelated reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia michael j. Proposal for the inclusion of pege coli asparaginase in. Hypersensitivity reactions to escherichia coli jaci. As a result, hypersensitivity to l asparaginase is a clinically relevant issue regardless of the source from which the drug was prepared. Treatmentlimiting reactions occurred in 9% of all patients, 14% of patients who had an allergic reaction to asparaginase, and 26% of patients who had an allergic reaction to both asparaginase and erwinia asparaginase. Pharmacokinetics of native escherichia coli asparaginase. Fatal hypersensitivity reactions hsrs occur in less than 1% of humans treated.
The goal of this activity is increased knowledge and competence of learners regarding the identification and management of asparaginase associated hypersensitivity reactions, including screening and management of silent inactivation, in pediatric and adolescent patients with acute lymphoblastic leukemia all. Among its multiple toxic effects, l asparaginase induces allergic reactions that may reduce its biological effect. Since these trials included patients who had previous hypersensitivity reactions to the native asparaginase, the possibility exists that crosssensitivity played a role in the reported reactions. Clinical utility and implications of asparaginase antibodies. Sample and clinical data collection was carried out from 576 paediatric. Lasparaginase is a cancer chemotherapeutic agent derived from escherichia coli.
Allergic reactions and antiasparaginase antibodies in children. Although hypersensitivity reactions to pegasp occur less frequently than with other formulations, they are not uncommon and have an adverse impact on patient outcomes. Sensitized mice developed high levels of anti asparaginase igg antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. The impact of hypersensitivity reactions on the duration of leukemiafree. L asparaginase asp is a key element in the treatment of paediatric acute lymphoblastic leukaemia all. Grade 2 or moderate hypersensitivity reactions mild bronchospasm. The national cancer institute has developed common toxicity criteria that can be used by health care providers to classify the severity of hypersensitivity reactions. Proposal for the inclusion of pege coli asparaginase in the. Sensitized mice developed high levels of antiasparaginase igg antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Coli asparaginase and substitution with erwinia asparaginase. Those who react to erwinia asparaginase may switch to pegasparaginase and usually tolerate it well. Nov 22, 2017 because adequate erwinase treatment requires an onerous thrice weekly schedule, and as many as one. Inflammatory response local, eliminates antigen without extensively damaging the hosts tissue. A desensitization protocol in children with lasparaginase.
There is an everincreasing number of therapeutics used to treat cancer. Hypersensitivity reactions to lasparaginase do not impact on. Pdf severe allergic reactions occur to lasparaginase, an important chemotherapeutic agent in treatment of childhood leukaemia. Predicting success of desensitization after pegaspargase. If wheezing or other symptomatic bronchospasm with or without urticaria, angioedema, hypotension, andor lifethreatening hypersensitivity reactions occur, discontinue asparaginase. Despite this large number, hypersensitivity reactions are not common except with platinum compound cisplatin, carboplatin, epipodophyllotoxins teniposide, etoposide, asparaginase, taxanes paclitaxel, and procarbazine. Backgroundl asparaginase is effective in the treatment of malignant diseases, but it has been associated with hypersensitivity reactions in 5% to 45% of the patients. Asparaginaseassociated toxicity in children with acute. The halflife of erwinia asparaginase is shorter than other forms of asparaginase, and the shorter halflife of erwinia asparaginase has demonstrated clinical implications, with the need for more frequent dosing every 23 days. Throughout the united states, nurses assume frontline responsibility for the assessment of asparaginase related hypersensitivity reactions. Hypersensitivity hypersensitivity reactions to pegaspargase, including lifethreatening anaphylaxis, can occur during therapy, including in patients with known hypersensitivity to e. History of serious pancreatitis with prior lasparaginase therapy history of serious thrombosis with prior lasparaginase therapy history of serious hemorrhagic events with prior lasparaginase therapy. Clinical hypersensitivity reactions against commercially available asparaginase have resulted in failure of asparaginase in treatment of all in more. Hypersensitivity was lower when native asparaginase was administered intramuscularly im compared with intravenous administration.
A recent publication listed 86 currently available antineoplastic medications. Pegaspargase is a mainstay in the treatment of acute lymphoblastic leukemia. Observe patients for 1 hour after administration in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis. Pharmacogenetics of asparaginase in acute lymphoblastic. History of serious thrombosis with prior l asparaginase therapy. Purposeto determine whether a desensitization protocol in children with native escherichia coli l asparaginase hypersensitivity allows. As a medication, l asparaginase is used to treat acute lymphoblastic leukemia all, acute myeloid leukemia aml, and nonhodgkins lymphoma. Pdf genomewide analysis links nfatc2 with asparaginase. The specific route of asparaginase administration may lead to disparate rates of hsrs and other adverse events in. Rates of clinical hypersensitivity to e coli asparaginase generally range from 10% to 30%, and with pegasparaginase rates range from 3% to 24% vrooman et al.
Effect of premedications in a murine model of asparaginase. To determine whether a desensitization protocol in children with native escherichia coli lasparaginase hypersensitivity allows subsequent safe administration of native e. There were less allergic reactions to erwinia asnase than native asnase. Other effects in patients taking l asparaginase include the possibility of hepatitis, pancreatitis, and altered production of coagulation factors resulting in either increased bleeding or increased clotting risk. Genomewide analysis links nfatc2 with asparaginase hypersensitivity. Hypersensitivity reactions can range from mild rashes and flushing to lifethreatening airway compromise and car diovascular collapse. Clinical hypersensitivity ranges from a mild local injection site reaction. Hypersensitivity reactions are unexpected and excessive responses of the immune system to a foreign substance antigen that cause a cascade of symptoms. Comparison of hypersensitivity reactions to pegasparaginase. For pegasp, a metaanalysis showed a reduction in hypersensitivity reactions when administration occurs by the im route, in comparison to the iv route, in pediatric patients under treatment for all. The risk of serious hypersensitivity reactions is higher in patients with known hypersensitivity to e.
Because adequate erwinase treatment requires an onerous thrice weekly schedule, and as many as one. It is given by injection into a vein, muscle, or under the skin. The risk of serious allergic reactions is higher in patients with known hypersensitivity to other forms of l asparaginase. Asparaginase agents are vital in the treatment of acute lymphoblastic leukemia all and can be delivered via an intravenous iv or intramuscular im injection. Oct 14, 2015 the halflife of erwinia asparaginase is shorter than other forms of asparaginase, and the shorter halflife of erwinia asparaginase has demonstrated clinical implications, with the need for more frequent dosing every 23 days. L asparaginase is an effective antineoplastic agent used in chemotherapy of all. Managing asparaginaserelated toxicity in adult patients. History of serious hypersensitivity reactions to erwinaze, including anaphylaxis. When intravenous iv infusion replaced intramuscular im injection as the standard route of administration, there were early reports suggested an increased hypersensitivity reactions hsrs rate. Asparaginase dosing, monitoring, and toxicity management. Sensitized mice had complete inhibition of plasma asparaginase activity p 4.
Earn 1 contact hour free of charge the goal of this ce activity is to provide nurses and nurse practitioners with knowledge and skills to recognize and manage acute hypersensitivity reactions hsrs occurring as a result of medication administration. Apr 27, 2014 asparaginase is an essential component of pediatric acute lymphoblastic leukemia all therapy. There are two forms of hypersensitivity seen in clinical practice. Clinical hypersensitivity reactions appear to be less prevalent with pegasparaginase, with rates from 324% reported in clinical trials 3,7,24,26. Hypersensitivity reactions types i, ii, iii, iv april 15, 2009. History of serious hemorrhagic events with prior l asparaginase therapy. May continue dosing for urticaria without bronchospasm, hypotension, edema, or need for parenteral intervention. Neutralising anti asparaginase antibodies can develop without a clinical allergic reaction and is known as silent hypersensitivity. Differentiating hypersensitivity versus infusionrelated reactions in. Our aim was to investigate genetic variants that may influence the risk to escherichia coliderived asp hypersensitivity. History of serious pancreatitis with prior l asparaginase therapy. Microbial asparaginase is an essential component of chemotherapy for the treatment of childhood acute lymphoblastic leukemia call.
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