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Re‐exploring immune‐related side effects of docetaxel in an observational study: Blood hypereosinophilia

机译:在一项观察性研究中重新探索多西他赛的免疫相关副作用:血液嗜酸性粒细胞增多

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摘要

Docetaxel is a major anticancer drug that can induce hypersensitivity reactions leading to deleterious treatment interruptions. Blood hypereosinophilia could be a biological sign, potentially lethal, of delayed visceral hypersensitivity reactions. We hypothesized this biological event is probably underreported. In this prospective observational study, we followed up 149 patients treated with docetaxel monotherapy for breast or lung cancer. For each patient, blood eosinophil counts were recorded during docetaxel treatment and up to 3 months after the end of docetaxel treatment. For all patients, blood eosinophil counts significantly increased under docetaxel chemotherapy (P < 0.01). Seven percent had persistent eosinophilia after the end of treatment. Four patients had blood eosinophil counts over 1000/mm3 with severe cardiac, cutaneous and digestive toxicities, and docetaxel imputability was confirmed using drug‐imputability scales. For two of these four patients, tissue biopsies were performed during the time of hypereosinophilia and of severe toxicities. Specific immunostainings and electron microscopy found numerous degranulating mast cells and eosinophils. Our study demonstrated that eosinophilia is frequent under docetaxel and could lead to severe complications, implicating eosinophils and mast cells, and possibly IgE. One way of treating hypersensitivity reactions could be by targeting IgEs with omalizumab, an anti‐IgE monoclonal antibody approved for the treatment of severe allergic asthma, and successfully used in food and poison‐induced anaphylactic reactions.
机译:多西他赛是一种主要的抗癌药物,可引起超敏反应,导致有害的治疗中断。血液嗜酸性粒细胞增多可能是内脏超敏反应延迟的生物学信号,可能致命。我们假设此生物学事件可能未被报道。在这项前瞻性观察性研究中,我们随访了149例接受多西他赛单药治疗的乳腺癌或肺癌患者。对于每位患者,在多西他赛治疗期间以及多西他赛治疗结束后最多3个月内记录血液嗜酸性粒细胞计数。对于所有患者,在多西他赛化疗后血中嗜酸性粒细胞计数显着增加(P <0.01)。治疗结束后,有7%的患者持续存在嗜酸性粒细胞增多。 4名患者的嗜酸性粒细胞计数超过1000 / mm 3 ,具有严重的心脏,皮肤和消化系统毒性,并使用药物可摄入量表确认了多西他赛的可插性。对于这四名患者中的两名,在高嗜酸性粒细胞增多和严重毒性期间进行了组织活检。特定的免疫染色和电子显微镜发现大量脱颗粒的肥大细胞和嗜酸性粒细胞。我们的研究表明,在多西他赛治疗下嗜酸性粒细胞增多是经常发生的,并可能导致严重的并发症,涉及嗜酸性粒细胞和肥大细胞,甚至可能涉及IgE。一种治疗超敏反应的方法是,以奥马珠单抗靶向IgE,奥马珠单抗是一种抗IgE单克隆抗体,已被批准用于治疗严重的过敏性哮喘,已成功用于食物和毒物引起的过敏反应。

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