Evaluation of Basophil CD203c as a Predictor of Carboplatin-Related Hypersensitivity Reaction in Patients with Gynecologic Cancer

Abstract

The incidence of hypersensitivity reaction (HR) to carboplatin has been reported to increase after repeated use of the drug. However, a reliable ex vivo test to predict HR to carboplatin is not currently available. We evaluated the clinical usefulness of measuring basophil CD203c to predict carboplatin-related HR in this prospective case-control study conducted at Mie University Hospital between October 2009 and September 2010. Eleven patients had history of carboplatin-related HR within the past 3 years, and 19 had no history of HR after receiving more than 5 courses of carboplatin therapy. Six of these 19 patients developed carboplatin-related HR during the study period. The CD203c basophils (%) and the mean fluorescence intensity (MFI) were analyzed on a flow cytometer and compared between patients with and without HR. Changes in the CD203c expression on basophils before and after HR were also assessed in patients who developed HR during the study period. The median CD203c basophils (%) and ΔMFI after 30-min exposure to 50 µg/mL carboplatin were significantly higher in patients with HR (3.5% and ΔMFI 9.0) compared with those without (2.2% and ΔMFI 0.4) (p<0.05). In particular, these values were significantly higher in patients with grade 4 anaphylaxis (10.6% and ΔMFI 22.0). All five patients who developed grade 2-4 anaphylaxis during the study period had high CD203c basophils (%) and/or increased ΔMFI on the day before HR. The results suggest that basophil CD203c may be a promising biomarker for the prediction of severe carboplatinrelated anaphylaxis.

The Contribution of the Basophil Activation Test to the Diagnosis of Hypersensitivity Reactions to Oxaliplatin

“…Data analysis was performed by FlowJo (TreeStar, Ashland, OR, USA). BAT was considered positive when there was an SI ≥2 and/or a basophil activation percentage > 2% [16,17,[19][20][21]. We compared basophil activation percentage and SI (for CD63 and CD203c expression) between patients and controls.…”

“…BAT has also been studied as a possible diagnostic method, given the role of basophils and mast cells as key cells in immediate hypersensitivity reactions. Viardot-Helmer et al [15] found an increased expression of CD63 with exposure to cisplatin; Iwamoto et al [16][17][18] and Jean-Luc [19] detected increased expression of the CD203C marker after incubation with carboplatin and oxaliplatin, respectively; Giavina-Bianchi et al [20] evaluated CD63 and CD203c expression in patients submitted to rapid drug desensitization (RDD) with oxaliplatin and carboplatin, obtaining positive results in 73% of patients. Due to the existing limitations of skin tests, further studies are essential to ascertain the role of the in vitro diagnostic methods, particularly BAT, in hypersensitivity reactions to platinum compounds, as well as to make comparisons with controls in order to gain a better understanding of the underlying immunological mechanisms.…”

Efficacy and Safety of Infliximab Tolerance Induction in Patients with Inflammatory Bowel Diseases who Experienced Acute Infusion Reactions

“…Interestingly, the only 2 patients with positive IDT had simultaneously a positive BAT. In the literature, BAT exhibits a good sensitivity and an excellent specificity in the diagnosis of allergy to drugs (e.g., antibiotics or cytotoxic chemotherapy) [24,39,40], but data concerning BAT in the context of IHR to monoclonal antibodies are largely lacking [41,42]. In our study, 2 out of the 3 patients who had positive BAT successfully received subsequent IFX infusions after induction of tolerance.…”

Pharmacovigilance in oncology: pattern of spontaneous notifications, incidence of adverse drug reactions and under-reporting

“…Even with the administration of therapeutic doses, plasma levels can be altered by deviations in product quality, genetic polymorphism, exaggerated sensitivity of the target tissue, drug interactions, and hepatic and renal dysfunctions. In contrast, no reaction was classified as doubtful, since many are described in the literature and package insert, such as vancomycin and urticarial reaction (Perrin-Lamarre et al, 2010), cisplatin and nephrotoxicity (Yao et al, 2007), carboplatin and anaphylaxis (Iwamoto et al, 2012), bleomycin and Stevens-Johnson syndrome (Giaccone et al, 1986), and etoposide and hypersensitivity reaction (Lindsay, Gaynon, 2012).…”