Background
Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a ...new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin‐specific immunoglobulin E (IgE) as a novel diagnostic tool.
Methods
Prospective, observational, longitudinal study with patients who, for a 1‐year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin‐reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol.
Results
Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin‐reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin‐specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points.
Conclusions
In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin‐specific IgE determination could be helpful.
Summary
Background Leukotrienes (LTs) appear to be crucial mediators of aspirin (ASA)‐induced lower respiratory tract reactions. Therefore, it is logical to assume that leukotriene‐modifier drugs ...(LTMDs) might block these reactions.
Objective The aim of this study was to determine whether concomitant treatment with LTMDs was associated with a reduction of ASA‐provoked lower respiratory tract reactions in patients with aspirin‐exacerbated respiratory disease (AERD), when compared to AERD patients who were not treated with LTMDs. Secondly, if ASA‐induced lower respiratory tract reactions were prevented in LTMD‐treated patients, was there then a higher prevalence of upper respiratory reactors or, alternatively, a higher prevalence of blocked reactions (‘non‐reactors’) in this group.
Methods Of 271 patients suspected by history of having AERD, 96 were taking cys‐LT receptor antagonists (cys‐LTRAs) and 12 were taking zileuton at the time of oral ASA challenges. A matched control group of 163 patients was not receiving LTMDs. All subjects underwent standard oral ASA challenges. Reactions were classified as follows: classic naso‐ocular combined with a 20% or > decline in forced expiratory volume of 1 s (FEV1); pure lower (20% or > decline in FEV1 without naso‐ocular); partial asthma (naso‐ocular + 15–20% decline in FEV1); upper only (naso‐ocular with < 15% decline in FEV1); negative (no reactions).
Results In patients treated with cys‐LTRAs, there were significant reductions in numbers of patients with ASA‐induced bronchospastic reactions and a concomitant increase in upper respiratory reactors. There were no significant differences in mean provoking doses of ASA or the percent changes in FEV1 values in both groups. In the 12 patients receiving zileuton, no reactions to ASA (16%) were similar to the cys‐LTRA‐treated group (11%) and the control group (15%).
Conclusion During oral ASA challenges, LTMD treatment appeared to shift target organ responses from both upper and lower respiratory tracts to upper tract alone. LTMD blocking of the entire respiratory tract did not appear to occur.
Background
Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard ...diagnostic tool (prior to desensitization).
Methods
Prospective, observational, longitudinal study with patients who, during a 3‐year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin‐specific IgE was determined in oxaliplatin‐reactive patients (who underwent DPT regardless of oxaliplatin‐specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables.
Results
A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty‐four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin‐specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5.
Conclusions
These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30–56% of patients, depending on culprit‐drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin‐specific IgE and oxaliplatin‐ST in the largest series of oxaliplatin‐reactive patients reported to date (74 oxaliplatin‐reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans.
Little information is available on the clinical efficacy of sublingual immunotherapy (SLIT) using extracts derived from mammalian epithelia. To assess clinical efficacy of cat SLIT based on natural ...exposure challenge test (NCT). Fifty cat allergic patients with rhinoconjunctivitis with or without asthma were included in a randomized double blind placebo controlled clinical trial of cat SLIT during 1 year. Twenty-five patients received active treatment and 25 placebo. Sublingual immunotherapy efficacy was assessed by natural exposure challenge to a cat in a cat-room and by skin tests. Airborne Fel d 1 levels, symptom scores and peak expiratory flow (PEF) values were monitored. Thirty-three (66%) out of 50 patients completed the treatment. Fel d 1 content of the maximum concentration was 0.51 μg per ml. During the build up phase, the accumulated dose was 1.7 μg of Fel d 1 and during the entire length of the study was 17.1. No adverse reports were reported. The active group showed a marked reduction (62%) in symptoms during the NCT (P < 0.001) with no changes in placebo group. Active group also showed a reduced PEF response to cat exposure (P < 0.05), and an improvement in skin test reactivity to a standardized cat extract (P < 0.05), without significant changes in placebo group. Mean Fel d 1 exposure during the NCT was 6.2 ± 2.21 ng/m³. The results suggest that the cat SLIT used in this study was able to improve cat allergy based on natural exposure challenge.
Background: Aspirin desensitization treatment is an option to decrease disease activity and reduce the need for systemic corticosteroids in patients with aspirin-exacerbated respiratory disease ...(AERD). Objective: This study was designed to determine whether the clinical courses of patients with AERD improved as early as 6 months after starting aspirin desensitization and to compare this with follow-up evaluations after at least a year. Methods: Between 1995 and 2000, 172 patients with AERD were admitted to our General Clinical Research Center, were desensitized to and treated with aspirin, were discharged to their home communities, and participated in follow-up interviews and written assessments of their clinical courses. Results: By the first 6 months of aspirin treatment, there were significant reductions in sinus infections and numbers of short courses of prednisone and improvements in sense of smell and general assessment of nasal-sinus and asthma symptoms (P < .0001). These results persisted for 1 to 5 years (P < .0001). Mean prednisone doses decreased from 10.8 mg/d to 8.1 and 3.6 mg/d at 6 months and greater than 1 year, respectively. Of the 172 patients, 24 (14%) discontinued aspirin treatment because of side effects, and 115 (67%) responded to aspirin treatment. After eliminating those who discontinued aspirin treatment because of side effects, the improvement rate was 115 (78%) of 148 patients. Of the 126 patients who completed a year or more of aspirin treatment, 110 (87%) experienced improvement. Conclusion: Aspirin desensitization followed by daily aspirin is efficacious by at least the first 6 months of treatment and continues to be effective for up to 5 years of follow-up. (J Allergy Clin Immunol 2003;111:180-6.)
Oxaliplatin hypersensitivity reactions may affect prognosis by jeopardizing the timely completion of the scheduled treatment sessions, or by forcing reactive patients into unexpected changes in ...therapy. Rapid Drug Desensitization (RDD) allows these patients to safely receive their first-choice treatments. However, the possible effects of RDD on the efficacy of oxaliplatin has never been studied. Objective: The objective of this study is to evaluate the effect on survival rates of RDD in oxaliplatin-hypersensitive patients.
7-year retrospective study comparing survival between oxaliplatin-hypersensitive case patients (receiving oxaliplatin by RDD) and non-allergic control patients (receiving standard oxaliplatin infusions). The primary endpoint of this study was Overall Survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons).
OS was 23.7 months (95%CI:15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143) it was 34.5 months (95%CI:21.7-55.5). There were no significant differences between both groups (HR1.42;95%CI:0.93-2.17;p=0.104).
Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD were not significantly different compared to those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients.
Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and ...highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.
Summary
Background
Immunotherapy (IT) with modified allergens reduces allergic rhinitis (AR) symptoms and medications requirements. Improvement of quality of life (QOL) is a key point in the ...treatment of AR. The aim of this study was to provide evidence of changes related to the patient's QOL (well‐being) induced by a modified (depigmented glutaraldehyde‐polymerized) therapeutic vaccine and of its safety.
Material and Methods
Fifty‐three patients with a well‐documented clinical history of seasonal AR sensitized to Dactylis glomerata and Olea europaea pollens were included in a randomized clinical trial. Twenty‐five patients (Group‐A) received a mixture of D. glomerata and O. europaea pollen extracts and 28 patients received placebo (group‐C). Any adverse event was recorded and graded in accordance with EAACI guidelines. RQLQ was recorded before the treatment (pollen season 2000) and after 1 year of treatment (pollen season 2001). Dose–response skin prick test with each allergen extract was conducted at baseline and at the end of the study.
Results
Each patient received 17 injections during this period. All patients completed the trial and no systemic adverse reactions were recorded. Symptom scores (P<0.001) and medication requirements (P<0.001) were significantly reduced in the IT group during the pollen season. This patient group also experienced greater and statistically significant improvement in overall RQLQ score and in five of the seven domains, all of them surpassing the threshold of ‘minimal important difference’ of 0.5 points.
Conclusions
Results of this study provided evidence that IT with depigmented, glutaraldehyde‐modified allergen extracts was well‐tolerated and added beneficial effects to AR treatment in pollen allergic patients eliciting an improvement in QOL enough to justify a change in the patient's treatment.
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