Prior Hypersensitivity Reactions Research Articles

Desensitization using pegaspargase in the era of commercially available Erwinia: A single-institution report on efficacy, cost, and resource utilization.

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. Patients with a clinical hypersensitivity reaction to pegaspargase were identified. When due for their next dose, patients were admitted to the pediatric intensive care unit, bone marrow transplant unit, or oncology unit, and underwent desensitization utilizing a rigorous premedication and multistep dilution-based protocol. Serum asparaginase activity levels were drawn after desensitization to assess for therapeutic levels of enzyme activity. We identified 11 patients who underwent a total of 33 desensitizations to pegaspargase and calaspargase pegol-mknl. No patients experienced clinically significant hypersensitivity reactions necessitating stopping the infusion, nor administration of rescue medications. All serum asparaginase activity levels collected demonstrated enzyme activity levels above predefined therapeutic thresholds. Cost analysis revealed substantial savings when patients received asparaginase desensitization over the now commercially available asparaginase E. chrysanthemi (recombinant) rywn. Performing desensitization to pegaspargase in the pediatric acute lymphoblastic leukemia population is feasible, safe, and effective. It is financially advantageous over available alternative approaches, and requires fewer injections and presentations to care.

Clinical outcomes and management of contrast hypersensitivity in patients requiring repeated computed tomography imaging

Introduction: In collaboration with the Department of Rheumatology, Allergy and Immunology, our study aims to review the outcomes of and propose an improved workflow for the management of patients with prior hypersensitivity reactions to iodinated contrast media (ICM). Method: Outpatients coming for contrast-enhanced computed tomography (CECT) were stratified into 3 categories (definite, unconfirmed and inaccurate) based on likelihood of their contrast hypersensitivity label. Patients could be offered a different ICM, receive the same ICM, or be referred to an allergist for further evaluation. There were 4 outcomes: (1) alternative ICM tolerated; (2) same ICM tolerated again; (3) patient developed a hypersensitivity reaction to either alternative or original ICM; and (4) CECT was deferred until assessment by an allergist. Comparison was made pre- and post-intervention to see if patient outcomes were improved. Results: There were 132 patients who made a total of 154 visits (90.3% had documented contrast hypersensitivity). Post-intervention, the number of visits postponed for premedication decreased (81.0% to 34.7%). There was a reduction in hypersensitivity reactions (from 42.9% to 14.3%). Of the 12 patients assessed by the allergist, 6 could continue using the same or alternative ICM, 4 were advised to abstain from further contrast administration and 2 were pending testing with a third agent. Conclusion: Active intervention by the radiologist can decrease the number of postponed, converted or cancelled CECT studies as well as reduce the number of adverse allergic-like events. Direct collaboration between radiologist and allergist for specific cases may be helpful in patients who will likely need future/repeated CECTs. Keywords: Corticosteroid, hypersensitivity, ICM, iodinated contrast media, premedication, skin testing

COVID-19 VACCINE REACTIONS AND SUSPECTED POLYETHYLENE GLYCOL ALLERGY: A PEDIATRIC CASE SERIES

<h3>Introduction</h3> Studies have demonstrated tolerance in high risk patients receiving Covid-19 m-RNA vaccines containing polyethylene glycol (PEG) with rare reactions.There is limited pediatric data regarding safety in receiving PEG containing Covid-19 vaccines with a history of prior hypersensitivity reactions to PEG containing chemotherapy (PEG-CTX). <h3>Methods</h3> Retrospective chart review from referred Pediatric Oncology patients with a history of prior reactions to PEG-CTX (01/2020-04/2022). Selective skin testing was completed using PEG molecular weigh 3350 and m-RNA Covid-19 vaccines with controls. <h3>Results</h3> Four pediatric patients (≤18 years old) had evidence suggestive of an immediate, hypersensitive reaction to PEG-CTX following treatment for acute lymphoblastic leukemia (ALL). All 4 patients experienced prior reactions to chemotherapy (L-Asparaginase). Symptoms included: hypotension, flushing, urticaria, angioedema, emesis and tachycardia. Due to prior reactions, these high-risk patients were not administered PEG containing Covid-19 vaccines due to safety concerns. Non-PEG containing Covid-19 vaccines were not approved for use in pediatric patients. Allergy skin testing (skin prick and intradermal) was completed in all four patients. One of 4 patients tested positive to both PEG and PEG containing Covid-19 vaccine. The 3 negative patients were administered PEG containing Covid-19 vaccine with monitoring for one hour without symptoms. <h3>Conclusion</h3> Pediatric patients in our study with prior reactions to PEG-CTX tolerated PEG containing Covid-19 vaccines. Further studies are needed in assessing PEG allergy in high-risk patients with a past history of reactions to PEG-CTX.

Pharmacological Prevention of Hypersensitivity Reactions Caused by Iodinated Contrast Media: A Systematic Review and Meta-Analysis.

Objectives: Hypersensitivity reactions (HSRs) are uncommon but serious adverse events following the administration of iodinated contrast media (ICM) prior to CT imaging. While premedication is almost universally given in high-risk patients, there is a lack of evidence regarding the efficacy of such premedication. This study aims to determine the efficacy of premedication with corticosteroids prior to ICM administration in the prevention of HSRs through meta-analysis. Materials and Methods: An extensive review of the literature yielded 404 potentially relevant studies. Of these, five studies met the inclusion criteria of this meta-analysis. Pooled HSR event rates were obtained from each of the studies for both patients who had and who had not received premedication with corticosteroids. Heterogeneity between studies was also determined. Results: A total of 736 patients across all five studies were included in the analysis. Patients who did not receive premedication had initial pooled HSR rates of 0.16 (95% CI, 0.07–0.35) across all studies. Following premedication, pooled HSR rates dropped to 0.02 (95% CI, 0.01–0.06). Patients who had prior HSRs were significantly less likely to experience HSRs (OR = 0.09; 95% CI, 0.03–0.25; p < 0.00001) after treatment with premedication. Conclusions: This meta-analysis offers evidence for the reduction in the recurrence of moderate and severe HSRs in patients who have a history of such reactions. Premedication with corticosteroids prior to ICM administration is thus highly recommended in high-risk patients.

Safety and efficacy of an outpatient 12-step desensitization protocol for antineoplastic agents

ObjectiveAntineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to such agent. Although desensitization protocols can be used to...

Prospective Mid-Term Results of a Completely Metal-Free Ceramic Total Knee Endoprosthesis: A Concise Follow-Up of a Previous Report

BackgroundHypersensitivity reactions are suspected to cause premature aseptic loosening in susceptible patients after total knee arthroplasty. In response, metal-free implants have been developed. The aim of this prospective, observational midterm study was the assessment of a completely metal-free ceramic knee replacement system as a concise follow-up of a previous report. MethodsThirty-eight patients, with anamnestic suspected or documented allergy to the metal used in prosthetic alloys, participated in this 4-year follow-up of the metal-free BPK-S (Peter Brehm) total knee replacement system with ceramic femoral and tibial components. Clinical assessment included Knee Society Score (KSS), Oxford Knee Score, Euro Quol-5D-Visual Analogue Scale (EQ-5D-VAS), and perioperative or postoperative complications and need for revision. The position of the implant, signs of loosening, and leg alignment were assessed radiographically. ResultsAll postoperative clinical scores improved significantly from baseline to 48-month follow-up examination. The Oxford Knee Score improved from 39 to 15 points. The KSS improved from 99 to 195 points (the KSS knee score 42.5 to 96 and the KSS function score 60 to 100). The EQ-5D improved from 12 to 7 points; the EQ-VAS improved from 52.5 to 97 points. No allergic reactions could be detected. Radiologically, a median preoperative varus deformity of 5° improved to 0° at 4-year follow-up. Radiolucent lines appeared around uncemented areas with no clinical symptoms. ConclusionThe fully metal-free BPK-S Integration ceramic knee replacement system exhibits excellent immuno-allergological compatibility, offering a safe option for patients with prior hypersensitivity reactions to metallic materials. Full cementation of all components is recommended to avoid radiolucent lines around the implant.

DRESS induced by amoxicillin-clavulanate in two pediatric patients confirmed by lymphocyte toxicity assay

BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious delayed hypersensitivity reaction that can be caused by antibiotic exposure. The reaction typically develops in 2 to 6 weeks. The pathophysiology is thought to involve toxic drug metabolites acting as a hapten, triggering a systemic response. The diagnosis is made clinically but can be confirmed using assays such as the lymphocyte toxicity assay (LTA), which correlates cell death upon exposure to drug metabolites with susceptibility to hypersensitivity reactions.Case presentationsCase 1 involves a previously healthy 11-month-old male with first exposure to amoxicillin-clavulanate, prescribed for seven days to treat a respiratory infection. The patient developed DRESS fourteen days after starting the drug and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Parental samples were also tested, showing both maternal and paternal susceptibility. Neither parent reported prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. The parents were advised to avoid penicillin class antibiotics and be monitored closely for DRESS if they are exposed.Case 2 involves an 11-year-old female with atopic dermatitis with first exposure to amoxicillin-clavulanate, prescribed for ten days to treat a secondary bacterial skin infection. She developed DRESS eleven days after starting antibiotics and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Maternal samples were also tested and showed sensitivity. The mother reported no prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy.ConclusionsAmoxicillin-clavulanate is a commonly used antibiotic and the cases we have described suggest that it should be recognized as a potential cause of DRESS in pediatric patients. Furthermore, these cases contribute to current literature supporting that there may be a shorter latent period in DRESS induced by antibiotics. We have also shown that the LTA can be a helpful tool to confirm DRESS reactions, and that testing may have potential implications for family members.

Safety of Off-Label Use of Ferumoxtyol as a Contrast Agent for MRI: A Systematic Review and Meta-Analysis of Adverse Events.

Ferumoxytol has been studied as an alternative to gadolinium-based MRI contrast agents, but regulatory body warnings currently limit its use. Estimate the adverse event rate in patients undergoing MRI with ferumoxytol as a contrast agent. Systematic review. Thirty-nine studies including 5411 ferumoxytol administrations in 4336 patients. Multiple databases were searched for studies using ferumoxytol as an off-label MRI contrast agent in any patient population as of April 2020. Studies were eligible for inclusion if they reported the number and severity of adverse events (classified by American College of Radiology [ACR] severity of acute reactions). Risk of bias was assessed using the ROBINS-I tool. The proportion of administrations with adverse events was calculated using random effects meta-analysis of proportions. No deaths related to ferumoxytol administration were reported. Sixteen studies reported immediate adverse events in 3849 patients undergoing 4901 ferumoxytol administrations. Ninety-seven immediate adverse events were reported and the pooled adverse event proportion for immediate adverse events was 0.02 (95% confidence interval [CI] 0.02-0.02). Twenty-three studies reported time-unspecified adverse events in 487 patients undergoing 510 ferumoxytol administrations. Five time-unspecified adverse events were reported; the pooled adverse event proportion for time-unspecified adverse events was 0.01 (95% CI 0.00-0.04). 88% of adverse events were mild (90/102), 11% (11/102) were moderate, and 1% (1/102) was severe. Sixteen studies were at low risk of bias, 23 studies were at serious risk of bias. Subgroup analysis by patient population revealed no significant variability (adult vs. pediatric). No studies evaluated the use of ferumoxytol as an alternative to patients who had a prior hypersensitivity reaction to gadolinium-based contrast agents (GBCAs). The overall adverse event rate for off-label ferumoxytol use as an MRI contrast agent is 2%, with rare severe reactions and no deaths. To date, there are no studies evaluating the safety of ferumoxytol as an alternative to GBCAs in patients with a prior hypersensitivity reaction. 2 TECHNICAL EFFICACY STAGE: 5.

Breakthrough Hypersensitivity Reactions to Gadolinium-based Contrast Agents and Strategies to Decrease Subsequent Reaction Rates: A Systematic Review and Meta-Analysis.

Background Hypersensitivity reactions to gadolinium-based contrast agents (GBCAs) that occur despite corticosteroid premedication (breakthrough reactions) are not well understood. Purpose To determine the GBCA breakthrough reaction rate overall and according to GBCA class and to determine the effect of using an alternative GBCA or allergy skin testing on the risk of a breakthrough reaction. Materials and Methods In this systematic review and meta-analysis, MEDLINE (from 1946 to 2019), Embase (from 1947 to 2019), and the Cochrane Central Register of Controlled Trials (2019 only) were searched for patients with a breakthrough reaction to a GBCA who were undergoing repeat GBCA administration. Breakthrough reaction rates were determined with random-effects modeling and meta-regression. Secondary analyses of GBCA class, switching to an alternative GBCA, and allergy skin testing were assessed. Quality Assessment of Diagnostic Accuracy Studies 2 was used to determine risk of bias and applicability. Percentages are meta-regression results and do not directly reflect raw data. Results Of the 148 identified studies, 23 were included, encompassing 120 patients and 130 GBCA administrations. The overall breakthrough reaction rate was 39% (95% confidence interval [CI]: 30%, 49%; 37 of 103 administrations). Breakthrough reaction rates for macrocyclic (36%; 95% CI: 25%, 48%; 23 of 64 administrations) and protein-binding linear (31%; 95% CI: 1%, 94%; [one of seven administrations) GBCAs did not differ (P = .90). There were insufficient analyzable data for gadodiamide, gadoversetamide, and gadopentetate. Hypersensitivity reaction rate after switching GBCAs was 50% (95% CI: 21%, 79%; three of nine administrations) with and 71% (95% CI: 21%, 95%; four of five administrations) without corticosteroid premedication, which did not differ (P = .82 and P = .17, respectively) from the observed rate when using corticosteroid premedication and the same GBCA (36%; 95% CI: 26%, 48%; 37 of 84 administrations). Hypersensitivity reaction rate after allergy skin testing (17%; 95% CI: 7%, 29%; zero of 21 studies) did not differ when compared with use of the same agent with corticosteroid premedication (P = .10). Meta-analysis limitations were the small number of patients and the high risk of bias. Conclusion Patients with a prior hypersensitivity reaction to a gadolinium-based contrast agent (GBCA) often had breakthrough reactions. The effect of switching to an alternative GBCA or using allergy skin testing to decrease reaction risk lacked enough available data for meaningful comparisons. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Prince in this issue.

PEGylated E. coli asparaginase desensitization: an effective and feasible option for pediatric patients with acute lymphoblastic leukemia who have developed hypersensitivity to pegaspargase in the absence of asparaginase Erwinia chrysanthemi availability

Asparaginase is an important component of multi-agent chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). Hypersensitivity to the PEGylated form, pegaspargase, is the most common toxicity observed and is ideally addressed by substituting multiple doses of erwinia asparaginase for each subsequent dose of pegaspargase. An international shortage of erwinia asparaginase has limited the therapeutic options for those experiencing pegaspargase hypersensitivity. Here, we report pegaspargase can be safely administered, while maintaining sustained levels of asparaginase activity, to patients who have had a prior hypersensitivity reaction to pegaspargase by using a standard rapid desensitization protocol. Ten patients with prior hypersensitivity reactions to pegaspargase were treated by using a standardized rapid desensitization protocol. Eight patients had therapeutic asparaginase levels between days 4 and 7 of ≥0.05 IU/mL, and seven patients continued to have sustained levels above ≥0.1 IU/mL between days 10 and 14. Based on chemotherapy regimens, five of these patients successfully received more than one dose of pegaspargase utilizing this protocol.

Medication-related anaphylaxis treated in hospital: Agents implicated, patient outcomes, and management lessons.

On background of increasing medication-related anaphylaxis rates in Australia, our aim was to determine epidemiology, outcomes, adverse drug reaction (ADR) reporting rates, and accuracy of coding in patients treated for nonantimicrobial medication-related anaphylaxis in our hospital network. From January 2010 to December 2015 patients treated in our hospital network for medication-related anaphylaxis were identified using International Classification of Diseases, 10th Edition diagnosis code T88.6. Cases were also extracted from the hospital ADR database. Medical records were reviewed to ensure consistent diagnosis and to extract clinical, documentation, and outcome data. Of 1110 patients coded as T88.6, 177 (15.9%) met the medication-related anaphylaxis definition. Eighty (40.8%) had anaphylaxis due to nonantimicrobial agents. Thirteen of these (16.3%) had a previous reaction to the same medication/group. In 51 (63.8%) patients, anaphylaxis occurred during inpatient stay, with 31 reactions occurring during surgery. Eighty-five medications were implicated, most commonly neuromuscular blocking agents (31, 36.5%) and nonsteroidal anti-inflammatory drugs. No trends were noted over the 6-year period, and there was no anaphylaxis-related mortality. Fifty-three (66.3%) patients were assessed in allergy clinics. One in 10 cases did not have the reaction documented in the discharge summary. Adverse drug reaction reports were received for 38 patients (47.5%). Although acute patient outcomes were excellent, gaps in practice were noted regarding ADR coding accuracy and reporting rates. One in 6 patients had a prior hypersensitivity reaction to a similar medication, so we recommend accurate documentation, ADR review with allergy follow-up, and patient held information to decrease re-exposure risk.

Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study

ObjectivesThe carboplatin desensitization (CD) protocol presented here allows patients with either a positive skin test or a prior hypersensitivity reaction (HSR) to safely, rapidly and effectively continue with carboplatin infusions. Newly described factors can identify patients at risk for developing adverse events during CD. MethodsA retrospective review was performed on patients with gynecologic cancer who underwent CD between 2005 and 2014. The CD protocol uses a four-step dilution process over 3.5h. Results129 patients underwent CD and completed a total of 788cycles. The desensitization protocol prevented HSRs in 96% (753 out of 788) of these cycles. Patients achieved an average of 6.1cycles (SD±4.55, range 0–23) with CD. The CD protocol allowed 73% (94 of 129) of the patients to undergo carboplatin infusion without reaction. Patients with moderate to life-threatening HSRs (grade 2 through 4) were 10.5years younger at initial CD than patients with grades 0 or 1 HSRs (52.3 vs. 63, P = 0.0307). One patient death occurred during her thirteenth desensitization cycle. The HSR in this case was complicated by pre-exisiting pulmonary hypertension. ConclusionsThis is the largest study of its kind showing a safe, effective and rapid (3.5h) CD protocol. The majority of patients with a history of either carboplatin hypersensitivity reaction or a positive skin test completed the CD protocol without HSRs. Age was identified as a risk factor for HSR severity during CD. Age can be employed along with pre-load dependent cardiac conditions as a way to help risk stratify patients undergoing CD.

A Safe and Novel Desensitization Protocol with Ferric Carboxymaltose to Treat Iron Deficiency Anemia.

Worldwide, iron deficiency anemia is the most common nutritional disorder. Treatment with oral iron supplementation may not be well tolerated due to gastrointestinal side effects. Therapy with Intravenous (IV) iron supplementation is more effective and better tolerated, especially in patients with underlying Inflammatory Bowel Disease (IBD) or malignancy. However, Hypersensitivity Reactions (HSR) and anaphylaxis to IV iron have been described. We evaluated the literature and developed an eleven step desensitization protocol for ferric carboxymaltose to be administered in high risk patients. We present the first case series demonstrating the safety of ferric carboxymaltose desensitization in patients with a history of anaphylaxis to IV iron and iron deficiency anemia. While there are many IV iron formulations available, ferric carboxymaltose can replenish iron stores with fewer doses. Ferric carboxymaltose is contraindicated in patients with prior hypersensitivity reactions to iron formulations. This novel eleven step desensitization protocol was well tolerated without any adverse reactions and allowed the patients to receive iron supplementation when limited therapeutic options existed.

How accurate is the label "allergic to iodinated contrast agents"?

Iodinated contrast agents (ICAs) are crucial to the use of many imaging studies. Reported allergies to ICAs in the medical record can interfere with optimal diagnostic imaging workups. To investigate the accuracy with which the label "allergic to ICAs" is applied. The medical records of 500 patients labeled "allergic to ICAs" at a single tertiary care hospital were reviewed. Patients were separated into three groups based on documentation in their medical records, as follows: Group 1, documented hypersensitivity reaction to ICAs; Group 2, documented ICA exposure with non-hypersensitivity adverse event (Group 2a) or without documented reaction (Group 2b); and Group 3, no documented prior exposure to an ICA. We then further reviewed the EMR to determine whether or not patients had subsequent administration of an ICA, whether or not they were given specific premedication, and whether or not they had a subsequent ICA-related event. A total of 16.6% of patients (n = 83) listed as "allergic to ICAs" had a documented hypersensitivity reaction following ICA administration (Group 1) while 58.6% (n = 293) of patients (Group 2) had a documented exposure to ICAs with either: (i) a non-hypersensitivity adverse event (23.5%, n = 69) or (ii) no record of a reaction to ICAs (76.5%, n = 224). The remaining 24.8% (n = 124), Group 3, had no record of exposure to an ICA, yet still carried the label. The majority of patients carrying the label "allergic to ICAs" had no record of a prior hypersensitivity reaction to ICAs.

Oxaliplatin salvage for recurrent ovarian cancer: A single institution's experience in patient populations with platinum resistant disease or a history of platinum hypersensitivity

ObjectiveHypersensitivity reactions can preclude platinum re-challenge for patients receiving second-line and higher carboplatin/cisplatin salvage therapy. The objective is to report our patient experience with oxaliplatin in recurrent or progressive epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC), including those with prior hypersensitivity reaction. MethodsA single institution, retrospective review from 1995 to 2012 of patients receiving oxaliplatin for treatment of recurrent or progressive EOC, PPC, or FTC was performed. Data collected included patient demographics, diagnosis date, prior chemotherapy regimens, platinum-free interval(s), prior hypersensitivity reactions, oxaliplatin toxicity, length of therapy, disease response, and last follow-up. Those who received ≥1cycles were included. A response to therapy was determined after ≥2cycles. ResultsForty-four patients were identified. All had prior carboplatin and 38.6% had prior cisplatin therapy. Twenty-three had a prior platinum hypersensitivity reaction. Patients received a median of 2 prior platinum containing regimens and 5 chemotherapy lines prior to oxaliplatin exposure. One patient experienced grade 3 pain. No grade 4 toxicities occurred. No treatment delays for pancytopenia noted. Nausea and dysesthesias were controlled medically and weren't dose-limiting. No nephropathy or neuropathy progressed on oxaliplatin or were dose-limiting. Disease response was observed in 43.2%. Of the responders, 36.8% had a prior platinum hypersensitivity reaction. Median number of 5cycles of an oxaliplatin containing regimen was given. Median follow-up was 15.5months. ConclusionsIn our experience, oxaliplatin is well tolerated and should be considered for platinum challenge after hypersensitivity even in patients with platinum resistant disease with a reasonable chance of response.

Abstract 1188: BRCA 1/2 mutation status is correlated with increased hypersensitivity reactions to carboplatin.

Abstract Background: Carboplatin (Cp) has become the standard first-line chemotherapeutic agent for treatment of ovarian cancer (OvCa), and Cp-related hypersensitivity reaction (HSR) has been observed in 5-20% of patients (pts). The several known potential risk factors for HSR include age, # of prior platinum treatments/cycles, and longer duration of platinum-free interval (PFI). The role of BRCA mutation status has not been studied in the context of Cp HSR, although OvCa pts with BRCAmut+ are treated repeatedly with platinum-based chemotherapies. Methods: The medical records of 74 women who enrolled and initiated at least one cycle of Cp on two phase I clinical trials (NCT01237067 and NCT01445418) with Cp and olaparib (AZD2281) were reviewed. Cp was given with olaparib for a maximum of 8 cycles. Clinical characteristics including BRCA mutation status, history of HSR prior to or on study, and outcomes were analyzed. Results: Primary diagnoses of the 74 pts were ovarian (71), fallopian tube (1), and primary peritoneal (2) carcinomas. Pts had a median age of 56 years (27-80) and ECOG 0-1. 50/74 (68%) pts were BRCA mutation carriers (BRCA 1 [38], BRCA 2 [10], BRCA1/2 [1], BRCApro 68% [1]). All pts had received platinum-based therapy prior to enrollment, and the median # of prior platinum regimens and cycles were 2 (1-6) and 12 (2-42), respectively. The median PFI from the last prior platinum treatment to the first Cp infusion on study was 15.3 months (6-82). 15/74 (20%) pts had a documented history of HSR to Cp prior to enrollment and were pre-medicated with methylprednisolone, H1, and H2 blockers before a slow, incremental Cp infusion. 15/74 (20%) pts developed HSR on study (grade 1 [6], grade 2 [5], and grade 3 [4]), 4 of whom had prior history of Cp HSR. Taken together, the incidence of Cp HSR at any point in the pts’ oncologic history, either prior to or on study, was 35.1% (26/74); prior history of Cp HSR was not predictive of HSR on study. Age, median # of prior platinum cycles, and PFI for the 15 pts with HSR on study vs. those with no HSR history were 52 (27-73) vs. 56 (34-73), 12 (6-20) vs. 10 (2-42), and 21.2 (8-53) vs. 15.3 (6-82), respectively, all of which were not statistically significant. 4/15 (27%) pts with HSR on study (including 2/4 pts with prior history) stopped Cp treatment due to repeated HSR despite pre-medications, while 7/15 (47%) pts stopped therapy for other reasons. The remaining 4/15 (27%) pts successfully completed 8 cycles or are continuing therapy per protocol. BRCA mutation was significantly associated with increased risk of HSR (prior to or on study), 46% (23/50), vs. 11% (2/19) for pts with no BRCA mutation (p = 0.010). Conclusions: Cp re-treatment can be successful for OvCa pts despite prior history of HSR. Prior HSR history did not increase the risk of HSR on study. Being a BRCAmut+ carrier was associated with a statistically significantly greater risk of HSR and may serve as a clinical predictive biomarker of Cp hypersensitivity. Citation Format: Dominic H. Moon, John L. Hays, Christina M. Annunziata, Anne M. Noonan, Lori Minasian, Nicole Houston, Elise C. Kohn, Jung-min Lee. BRCA 1/2 mutation status is correlated with increased hypersensitivity reactions to carboplatin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1188. doi:10.1158/1538-7445.AM2013-1188

381 Adverse Drug Reactions in Hospitalized Patients

BackgroundTo describe adverse drug reactions (ADRs) in hospitalized patients.MethodsA cross-sectional study with a questionnaire for adverse drug reactions based on European Network for Drug Allergy (ENDA) was performed. Hospitalized patients older than 12 years of age were included.ResultsA total of 150 patients were studied, 84 being female. Their ages ranged from 14 to 94 years, with an average of 55 years. The average number of medications per patient was 7.5. Fifteen ADRs were reported during hospitalization (10%). Five ADRs were classified as hypersensitivity, including 2 IgE-mediated reactions that were observed in 2 patients hospitalized for desensitization (anti-rabies vaccine and insulin). The procedure had to be suspended in these patients. Three non-IgE-mediated hypersensitivity reactions occurred: rash after non-steroidal anti-inflammatory drug (NSAID) intake, coughing and itching with angiotensin converter enzyme inhibitor (ACEI) and rash with iodinated contrast. The remaining patients (10) had common side effect reactions to several drugs. Twenty-eight patients have had prior hypersensitivity reaction, being five IgE-mediated (two with beta-lactam antibiotics, one with non beta-lactam antibiotic, one with insulin and the last one with rabies vaccine) and 23 non-IgE-mediated (8 with NSAIDs, 5 with ACEI, 3 with beta-lactam antibiotics, 3 with non beta-lactam antibiotics, 2 with iodinated contrast and 2 with other drugs). Most hypersensitivity reactions were cutaneous. In 3 patients, previous hypersensitivity reactions were not mentioned at the time of hospitalization.ConclusionsThe average number of medications administered per patient during hospitalization is high. Adverse drug reactions are very common and have great clinical relevance. Ten percent of patients presented ADRs during hospitalization and one third of them had hypersensitivity reactions, what is in accordance with literature.

An approach to natalizumab hypersensitivity: a case series of induction of tolerance

Induction of tolerance protocols have been applied successfully to manage allergic reactions to many medications. Hypersensitivity reactions to natalizumab (TYSABRI®) have been recognized as a growing problem. In circumstances where a hypersensitivity reaction to a medication has occurred, but no suitable alternative exists, drug induction of tolerance protocols may be considered. Drug induction of tolerance protocols were performed in three patients with prior hypersensitivity reactions to natalizumab. All three patients tolerated the protocol without adverse reactions, allowing for the safe reintroduction of natalizumab. To conclude, this case series demonstrates success with an induction of tolerance procedure to a highly effective biological agent for multiple sclerosis, in patients with allergic reactions to natalizumab.

Mandatory Influenza Vaccination of Health Care Workers: Translating Policy to Practice

Influenza vaccination of health care workers has been recommended since 1984. Multiple strategies to enhance vaccination rates have been suggested, but national rates have remained low. BJC HealthCare is a large Midwestern health care organization with approximately 26,000 employees. Because organizational vaccination rates remained below target levels, influenza vaccination was made a condition of employment for all employees in 2008. Medical or religious exemptions could be requested. Predetermined medical contraindications include hypersensitivity to eggs, prior hypersensitivity reaction to influenza vaccine, and history of Guillan-Barré syndrome. Medical exemption requests were reviewed by occupational health nurses and their medical directors. Employees who were neither vaccinated nor exempted by 15 December 2008 were not scheduled for work. Employees still not vaccinated or exempt by 15 January 2009 were terminated. Overall, 25,561 (98.4%) of 25,980 active employees were vaccinated. Ninety employees (0.3%) received religious exemptions, and 321 (1.2%) received medical exemptions. Eight employees (0.03%) were not vaccinated or exempted. Reasons for medical exemption included allergy to eggs (107 [33%]), prior allergic reaction or allergy to other vaccine component (83 [26%]), history of Guillan-Barré syndrome (15 [5%]), and other (116 [36%]), including 14 because of pregnancy. Many requests reflected misinformation about the vaccine. A mandatory influenza vaccination campaign successfully increased vaccination rates. Fewer employees sought medical or religious exemptions than had signed declination statements during the previous year. A standardized medical exemption request form would simplify the request and review process for employees, their physicians, and occupational health and will be used next year.

Successful desensitization to oxaliplatin with incorporation of calcium gluconate and magnesium sulfate

Since the results of the MOSAIC trial demonstrated an improved disease-free survival in stage III colorectal patients treated with oxaliplatin combined with 5-fluorouracil and folinic acid when they were compared with those treated with 5-fluorouracil and folinic acid alone, the addition of this organoplatin to 5-fluorouracil and folinic acid has become first-line adjuvant treatment for stage III colorectal cancer. Unfortunately, there is a small population of patients who develop grade III/IV hypersensitivity reactions to oxaliplatin which, until recently, have interfered with further treatment with oxaliplatin-containing regimens. Successful oxaliplatin desensitization protocols for patients having severe oxaliplatin hypersensitivity reactions have been reported. However, none of these protocols, have incorporated magnesium and calcium salts. Retrospective data has suggested that pretreating colorectal cancer patients with magnesium sulfate and calcium gluconate before the administration of oxaliplatin may reduce the incidence of neurotoxicities induced by this drug. Therefore, we modified a previously published oxaliplatin-desensitization protocol by incorporating intravenous calcium gluconate and magnesium sulfate, and report a patient with stage IIIc colorectal cancer and prior severe hypersensitivity reactions to oxaliplatin who underwent successful oxaliplatin desensitization using this protocol.