Department of Clinical Hematology, Montpellier University Hospital, Montpellier, France.
Hematology Federation of University Hospitals of Montpellier and Nîmes, University of Montpellier, Montpellier, France.
JAMA Netw Open. 2019 Apr 5;2(4):e192093. doi: 10.1001/jamanetworkopen.2019.2093.
Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in patients with lymphoma.
To examine the association of occupational exposure to pesticides with immunochemotherapy response and survival among patients treated for diffuse large B-cell lymphoma.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed patients treated from July 1, 2010, to May 31, 2015, for diffuse large B-cell lymphoma, with a 2-year follow-up. The study took place at 6 university and nonuniversity hospitals in Languedoc-Roussillon, France. A total of 404 patients with newly diagnosed diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy were included before the study began. Occupational history was reconstructed for 244 patients and analyzed with the PESTIPOP French job-exposure matrix to determine likelihood of occupational exposure to pesticides. Analysis of the data was performed from July 15, 2017, to July 15, 2018.
Treatment failure (ie, partial response, stable disease, disease progression, or interruption for toxic effects) rate, 2-year event-free survival, and overall survival between exposed and nonexposed patients after adjustment for confounding factors.
A total of 244 patients (mean [SD] age, 61.3 [15.2] years; 153 [62.7%] male) had complete occupational data. Of these patients, 67 (27.4%) had occupational exposure to pesticides, with 38 exposed through agricultural occupations. Occupational exposure was not associated with clinical and biological characteristics at diagnosis. Occupationally exposed patients had a significantly higher treatment failure rate (22.4% vs 11.3%; P = .03; adjusted odds ratio [AOR] for confounding factors, 3.0; 95% CI, 1.3-6.9); this difference was higher among patients with exposing agricultural occupations compared with other patients (29.0% vs 11.7%; AOR, 5.1; 95% CI, 2.0-12.8). Two-year event-free survival was 70% in the occupationally exposed group vs 82% in the unexposed group (adjusted hazard ratio [AHR] for confounding factors, 2.2; 95% CI, 1.3-3.9). Among patients with exposing agricultural occupations compared with other patients, the difference was more pronounced (2-year event-free survival, 56% vs 83%; AHR, 3.5; 95% CI, 1.9-6.5). Similarly, 2-year overall survival was lower in the group of patients with exposing agricultural occupations compared with other patients (81% vs 92%; AHR, 3.9; 95% CI, 1.5-10.0).
This retrospective study showed that agricultural occupational exposure to pesticides was associated with treatment failure, event-free survival, and overall survival among patients with diffuse large B-cell lymphoma.
重要性：职业性使用农药是罹患非霍奇金淋巴瘤的一个风险因素。农药和化疗的主要生物学机制是遗传毒性和活性氧的产生。接触低剂量遗传毒性和氧化化合物的患者可能会出现细胞适应性，从而影响淋巴瘤患者的化疗效果。
目的：研究职业性暴露于农药与接受弥漫性大 B 细胞淋巴瘤治疗的患者免疫化学疗法反应和生存之间的关联。
设计、环境和参与者：本回顾性队列研究评估了 2010 年 7 月 1 日至 2015 年 5 月 31 日期间在法国朗格多克-鲁西永接受蒽环类药物为基础的免疫化学疗法治疗的新诊断为弥漫性大 B 细胞淋巴瘤的患者，随访时间为 2 年。该研究在法国朗格多克-鲁西永的 6 所大学和非大学医院进行。在研究开始前，共纳入了 404 例接受新诊断为弥漫性大 B 细胞淋巴瘤且接受蒽环类药物为基础的免疫化学疗法治疗的患者，其中 244 例患者的职业史被重建，并通过 PESTIPOP 法国职业暴露矩阵进行分析，以确定职业性接触农药的可能性。数据分析于 2017 年 7 月 15 日至 2018 年 7 月 15 日进行。
主要结果和措施：在调整混杂因素后，暴露和非暴露患者的治疗失败率（即部分缓解、稳定疾病、疾病进展或因毒性作用而中断）、2 年无事件生存率和总生存率。
结果：共有 244 例患者（平均[标准差]年龄，61.3[15.2]岁；153[62.7%]为男性）具有完整的职业数据。这些患者中，67 例（27.4%）职业性接触过农药，其中 38 例通过农业职业接触农药。职业性接触与诊断时的临床和生物学特征无关。与未接触农药的患者相比，职业性接触农药的患者治疗失败率显著更高（22.4%比 11.3%；P = .03；混杂因素调整后优势比，3.0；95%置信区间，1.3-6.9）；与其他职业相比，接触农业职业的患者差异更为明显（29.0%比 11.7%；AOR，5.1；95%CI，2.0-12.8）。暴露组的 2 年无事件生存率为 70%，未暴露组为 82%（混杂因素调整后风险比，2.2；95%CI，1.3-3.9）。与其他职业相比，接触农业职业的患者差异更为明显（2 年无事件生存率，56%比 83%；AHR，3.5；95%CI，1.9-6.5）。同样，与其他职业相比，接触农业职业的患者的 2 年总生存率较低（81%比 92%；AHR，3.9；95%CI，1.5-10.0）。
结论和相关性：这项回顾性研究表明，弥漫性大 B 细胞淋巴瘤患者职业性接触农业用农药与治疗失败、无事件生存率和总生存率有关。
Zotero 插件