Indiana University – Purdue University Indianapolis

Alpha-Gal syndrome unveiled: decoding the glycan-driven red meat allergy.

α-Gal syndrome (AGS) is a type of allergy to red meat and other mammalian products that develops after a tick bite. Symptoms may include urticaria, angioedema, gastrointestinal and respiratory symptoms, and, most dangerously, anaphylactic shock. Among food allergies, it is considered unusual because: (i) the major allergen is not a protein, but a carbohydrate moiety Galα-1,3-Gal, which humans do not synthesize; (ii) it is caused by α-Gal-containing glycoconjugates injected during a tick bite; (iii) the hypersensitivity is effected by IgE antibodies which arise after a class switch from IgG and IgM-class antibodies; (iv) it seems to be triggered by α-Gal-containing glycolipids present in red meat, with delayed onset. Here, we evaluate glycans that may cause AGS, review the data about glycosyltransferases that synthesize α-Gal and related antigens and describe the immune mechanism behind AGS: sensitization and host response to ticks' saliva. In addition, we consider future research avenues that may lead to a better understanding and management of AGS as a modern dietary affliction rooted in an old evolutionary trade-off.

Correction to: Alpha-Gal syndrome unveiled: decoding the glycan-driven red meat allergy.

Incidence of cetuximab-related infusion reactions in oncology patients treated at the University of North Carolina Cancer Hospital.

The primary purpose of this study was to determine the rate of infusion reactions to cetuximab in oncology patients treated at the University of North Carolina Cancer Hospital. Secondarily, we sought to evaluate predictors of grade 3-4 hypersensitivity, including geography. Data were collected by retrospective chart review for patients treated with cetuximab at the University of North Carolina Cancer Hospital between 15 November 2006 and 31 December 2010. Data were analyzed for occurrence of hypersensitivity reaction in 125 patients with various cancer types. Of the 125 subjects, 31 (24.8%) experienced an infusion reaction of any grade. Of 125, 18 (14.4%) experienced a grade 3 or 4 reaction. The odds ratio for patients with an allergy history having a grade 3 or 4 reaction was 2.57 (95% CI 0.93 to 7.09, p = 0.07). Pretreatment with steroids was associated with absence of grade 3 or 4 reaction with an odds ratio of 0.21 (95% CI 0.05 to 0.83, p = 0.04). Mapping of reaction rates by county revealed higher rates in some of the more rural counties of North Carolina, however, statistical power was lacking. Rates of hypersensitivity reaction at UNC are similar to rates seen in other areas of the southeastern United States and higher than in other regions of the United States and Europe. Rates of both hypersensitivity reactions and grade 3 to 4 hypersensitivity reactions have not substantially changed over time. Geography, allergy history, and perhaps smoking or cancer type may help predict who will react to cetuximab. Steroids should be strongly considered as premedication in addition to diphenhydramine.

Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor.

To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Phase II, open-label clinical trial. Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation. Patients were required to have received irinotecan, either alone or in a combination regimen, and to have demonstrated clinical failure on this regimen before study entry. Cetuximab was administered weekly by intravenous infusion. The first dose of 400 mg/m(2) was given during the course of 2 hours. Subsequent weekly treatments were given at a dose of 250 mg/m(2) during the course of 1 hour. Fifty-seven eligible patients were treated. All were assessable for toxicity and response. The most commonly encountered grade 3 to 4 adverse events, regardless of relationship to study drug, were an acne-like skin rash, predominantly on the face and upper torso (86% with any grade; 18% with grade 3), and a composite of asthenia, fatigue, malaise, or lethargy (56% with any grade, 9% with grade 3). Two patients (3.5%) experienced grade 3 allergic reactions requiring discontinuation of study treatment. A third patient experienced a grade 3 allergic reaction that resolved, and the patient continued on the study. Neither diarrhea nor neutropenia were dose limiting in any of the 57 patients treated. Five patients (9%; 95% CI, 3% to 19%) achieved a partial response. Twenty-one additional patients had stable disease or minor responses. The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer is 6.4 months. Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Further studies of cetuximab will evaluate the use of cetuximab in conjunction with first-line and adjuvant treatments for this disease.