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