Silver Jared, Garcia-Neuer Marlene, Lynch Donna-Marie, Pasaoglu Gülden, Sloane David E, Castells Marianna
Division of Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
The Ohio State University College of Medicine, Columbus, Ohio.
J Allergy Clin Immunol Pract. 2020 May;8(5):1668-1680.e2. doi: 10.1016/j.jaip.2020.02.013. Epub 2020 Feb 26.
Oxaliplatin causes a wider variety of immediate hypersensitivity reactions than do other platin-based chemotherapeutics. Some resemble type 1 reactions that respond to desensitization. Others are atypical, possibly mast cell-independent cytokine release reactions refractory to desensitization. Given this variability, clinicians need an evidence-based strategy to personalize therapy for oxaliplatin-hypersensitive patients.
To develop a data-driven algorithm to optimize treatment of oxaliplatin-hypersensitive patients.
We retrospectively analyzed the baseline clinical characteristics, biomarkers, and reactions of 48 oxaliplatin-hypersensitive patients who received a total of 266 oxaliplatin desensitizations.
We characterized 4 endophenotypes: type 1, cytokine release, mixed, and either. A mean 40-fold increase in serum concentration of IL-6 helped define the cytokine release endophenotype. Younger patients were more likely to have a cytokine release endophenotype, whereas older patients were more likely to have a type 1 reaction. Skin testing was not informative for determining endophenotype or risk of reaction during desensitization, and did not associate with initial or desensitization grade of reaction. Patients with a history of atopy and an initial type 1 reaction responded to desensitization with antihistamine premedications, whereas nonatopic patients with the same initial reaction phenotype were more likely to convert to a cytokine release or mixed reaction during desensitization. We combined these reaction patterns with biomarker data and desensitization outcomes to construct an algorithm that helps tailor desensitization protocol design to meet individual patient needs.
Endophenotyping oxaliplatin hypersensitivity reactions may help forecast desensitization outcomes and personalize treatment plans.
与其他铂类化疗药物相比，奥沙利铂引起的即刻超敏反应种类更多。有些反应类似于对脱敏治疗有反应的1型反应。其他反应则是非典型的，可能是与肥大细胞无关的细胞因子释放反应，对脱敏治疗无效。鉴于这种变异性，临床医生需要一种基于证据的策略来为奥沙利铂超敏患者制定个性化治疗方案。
开发一种数据驱动的算法，以优化奥沙利铂超敏患者的治疗。
我们回顾性分析了48例接受了总共266次奥沙利铂脱敏治疗的奥沙利铂超敏患者的基线临床特征、生物标志物和反应。
我们确定了4种内表型：1型、细胞因子释放型、混合型和其他型。血清白细胞介素-6浓度平均增加40倍有助于定义细胞因子释放内表型。年轻患者更有可能具有细胞因子释放内表型，而老年患者更有可能出现1型反应。皮肤试验对于确定脱敏期间的内表型或反应风险并无帮助，且与初始或脱敏反应分级无关。有特应性病史且初始为1型反应的患者对使用抗组胺药进行预处理的脱敏治疗有反应，而具有相同初始反应表型的非特应性患者在脱敏过程中更有可能转变为细胞因子释放或混合反应。我们将这些反应模式与生物标志物数据和脱敏结果相结合，构建了一种算法，有助于定制脱敏方案设计以满足个体患者的需求。
对奥沙利铂超敏反应进行内表型分析可能有助于预测脱敏结果并制定个性化治疗方案。
