Department of Pharmacy, Mie University Hospital, and Department of Otorhinolaryngology-Head and Neck Surgery, Mie University, Graduate School of Medicine, Mie, Japan.
Biol Pharm Bull. 2012;35(9):1487-95. doi: 10.1248/bpb.b12-00150.
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 carboplatin-related anaphylaxis.
报道称,反复使用卡铂后,过敏反应(HR)的发生率会增加。然而,目前尚无可靠的体外试验来预测卡铂所致 HR。本前瞻性病例对照研究于 2009 年 10 月至 2010 年 9 月在日本 Mie 大学医院进行,评估了测量嗜碱性粒细胞 CD203c 预测卡铂相关 HR 的临床应用价值。11 例患者在过去 3 年内有卡铂相关 HR 史,19 例患者在接受 5 个以上卡铂疗程后无 HR 史。在此期间,这 19 例患者中有 6 例发生了卡铂相关 HR。采用流式细胞仪分析 CD203c+嗜碱性粒细胞(%)和平均荧光强度(MFI),并比较 HR 患者和无 HR 患者之间的差异。对研究期间发生 HR 的患者,还评估了 HR 前后嗜碱性粒细胞 CD203c 表达的变化。HR 患者(3.5%和ΔMFI 9.0)暴露于 50μg/ml 卡铂 30 分钟后 CD203c+嗜碱性粒细胞(%)和ΔMFI 的中位数明显高于无 HR 患者(2.2%和ΔMFI 0.4)(p<0.05)。特别是,4 级过敏反应患者(10.6%和ΔMFI 22.0)的这些值明显更高。在此期间发生 2-4 级过敏反应的 5 例患者,在发生 HR 前一天,CD203c+嗜碱性粒细胞(%)和/或ΔMFI 明显升高。结果表明,嗜碱性粒细胞 CD203c 可能是预测严重卡铂相关过敏反应的有前途的生物标志物。