title: Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization.
abstract: 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.
authors.affiliation: Allergy Division, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Alvarez-Cuesta
authors.affiliation: Allergy Division, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Madrigal-Burgaleta
authors.affiliation: Allergy Division, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Angel-Pereira
authors.affiliation: Allergy Division, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ureña-Tavera
authors.affiliation: Allergy Division, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Zamora-Verduga
authors.affiliation: Allergy Division, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Lopez-Gonzalez
authors.affiliation: Allergy Division, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Berges-Gimeno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001685:Biological Factors / Q000009:adverse effects*; D002648:Child; D003888:Desensitization, Immunologic; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin; D010641:Phenotype; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012882:Skin Tests; D055815:Young Adult
chemical_list: D000485:Allergens; D000970:Antineoplastic Agents; D001685:Biological Factors; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D007073:Immunoglobulin E
keywords: chemotherapy agents; desensitization; drug provocation test; oxaliplatin; specific IgE