Jappe U, Kolaly T, de Vries MS, Gülsen A, Homann A
Nutrients •
Sensitization to the carbohydrate antigen α-Gal is associated with allergic reactions against different types of food that contain α-Gal (e.g., mammalian meat). This form of allergy is termed α-Gal syndrome (AGS), and the diagnosis is challenging due to delayed symptom onset and cross-reactivity with multiple mammalian products. It is estimated that AGS is underdiagnosed, pointing to an unmet need for patient care. Sera from patients with suspected AGS based on clinical history were analyzed by ImmunoCAP and the IgE cross-reactivity immune profiling (ICRIP) system specifically developed by us. IgE from patient sera against different forms of α-Gal was analyzed using α-Gal-containing analytes and negative controls. Sera from 33 patients with suspected AGS were analyzed. Sera from 22 patients yielded a clearly positive signal (>0.35 kU/L) for IgE against α-Gal in ImmunoCAP. For 7 of the remaining 11 patients with negative or ambiguous (IgE level between 0.1 and 0.35 kU/L) results in ImmunoCAP, ICRIP analyses supported the suspected association of the allergy symptoms with IgE against α-Gal components. This component-resolved analysis helps the allergist to provide an individual diagnosis for each patient. The diagnosis of AGS is challenging. An interplay between clinical history and lab analysis via ImmunoCAP and the specifically developed ICRIP system helps patients and allergists in establishing the correct diagnosis, thereby preventing accidental exposure and recurrent AGS episodes.
Matuschek C, Bölke E, Belka C, Ganswindt U, Henke M, et al.
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] •
Close resection margins < 5 mm (CM) or extra capsular extent at the lymph nodes (ECE) impair the prognosis of patients with squamous cell cancer of the head and neck (SCCHN) scheduled for adjuvant radiochemotherapy. We conducted a multicenter phase II study to investigate toxicity and efficacy of additional cetuximab administered concomitantly and as maintenance for the duration of 6 months following adjuvant radiochemotherapy., Ppreliminary results on feasibility and acute toxicity on skin and mucosa are presented in this article. Patients with SCCHN following CM resection or with ECE were eligible for the study. In all, 61.6 Gy (1.8/2.0/2.2 Gy, days 1-36) were administered using an integrated boost intensity-modulated radiotherapy (IMRT) technique. Cisplatin (20 mg/m(2), days 1-5 and days 29-33) and 5-fluorouracil (5-FU) as continuous infusion (600 mg/m(2), days 1-5 + days 29-33) were given concurrently. Cetuximab was started 7 days prior to radiochemotherapy at 400 mg/m(2) followed by weekly doses of 250 mg/m(2). Maintenance cetuximab began after radiochemotherapy at 500 mg/m(2) every 2 weeks for 6 months. Of the 55 patients (46 male, 9 female, mean age 55.6, range 29-70 years) who finished radiochemotherapy, 50 were evaluable for acute toxicity concerning grade III/IV toxicities of skin and mucosa. Grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals were documented for 46, 28, and 14 % of patients, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 5 patients due to allergic reactions after the first application. In addition, 22 % of patients discontinued cetuximab within the last 2 weeks or at the end of radiochemotherapy. Of patients embarking on maintenance treatment, 80 % were still on cetuximab at 3 months and 63 % at 5 months. Concurrent and maintenance treatment with cetuximab could be administered as scheduled in 48 % of patients. Adjuvant radiochemotherapy with concomitant and maintenance cetuximab is feasible and acute toxicities are within the expected range. Compliance within the first 3-5 months is moderate.
Kuhnt T, Sandner A, Wendt T, Engenhart-Cabillic R, Lammering G, et al.
Annals of oncology : official journal of the European Society for Medical Oncology •
Cetuximab is active in the treatment of squamous cell carcinoma of the head and neck (SCCHN), enhancing both radiotherapy and chemotherapy effects. This phase I study was designed to investigate the safety and tolerability of combining weekly cisplatin treatment with cetuximab and hyperfractionated-accelerated radiotherapy (HART) for locally advanced SCCHN. Patients with unresectable stage III or IVA/B SCCHN were treated with cetuximab, 400 mg/m² initial dose on day -7 of HART, followed by 250 mg/m² weekly during the administration of HART, which started with 2.0 Gy/day (5 days/week) for 3 weeks followed by 1.4 Gy/twice-daily (Monday to Friday) for another 3 weeks, resulting in a total dose of 70.6 Gy. Cisplatin was administered weekly starting on the first day of radiotherapy until week 6. Cisplatin was dose escalated of four dose levels from 20 to 40 mg/m² using a classical 3 + 3 dose escalation algorithm. Eighteen patients were enrolled. Sixteen patients were eligible for toxicity, and 15 for response. No maximum tolerated dose was reached for cisplatin. One of six patients of dose level 4 had grade 4 neutropenia. This patient died 1 week after the end of the study treatment. The most common types of grade 3+ adverse events were mucositis (9 of 16 patients), in-field dermatitis (6 of 16 patients) and neutropenia (4 of 16 patients). Cetuximab-related hypersensitivity was observed in 1 out of 18 patients. Six weeks after the end of the study treatment, 5 complete responses, 8 partial responses and 1 progressive disease (at distant sites) were documented in a total of 15 patients (objective response rate 87%). The combination of cisplatin with cetuximab and HART is active, well tolerated and merits additional investigation. The recommended weekly dose of cisplatin for phase II studies is 40 mg/m².
Brinkmann N, Malissard M, Ramuz M, Römer U, Schumacher T, et al.
Bioorganic & medicinal chemistry letters •
The alpha-Gal trisaccharide Gal(alpha)(1-->3)Galbeta(1-->4)GlcNAc 11 was synthesized on a homogeneously soluble polymeric support (polyethylene glycol, PEG) by use of a multi-enzyme system consisting of beta-1,4-galactosyltransferase (EC 2.4.1.38), alpha-1,3-galactosyltransferase (EC 2.4.1.151), sucrose synthase (EC 2.4.1.13) and UDP-glucose-4-epimerase (EC 5.1.3.2). In addition workup was simplified by use of dia-ultrafiltration. Thus the advantages of classic chemistry/enzymology and solid-phase synthesis could be united in one. Subsequent hydrogenolytic cleavage afforded the free alpha-Gal trisaccharide.
