European and Latin American Environment, Survival and Childhood Cancer Network (ENSUCHICA), Spain; Pediatric Environmental Health Speciality Unit, Department of Pediatrics, Laboratory of Environment and Human Health (A5), Institute of Biomedical Research (IMIB-Arrixaca), Clinical University Hospital "Virgen de la Arrixaca", University of Murcia, Murcia, Spain.
European and Latin American Environment, Survival and Childhood Cancer Network (ENSUCHICA), Spain; Pediatric Environmental Health Speciality Unit, Department of Pediatrics, Laboratory of Environment and Human Health (A5), Institute of Biomedical Research (IMIB-Arrixaca), Clinical University Hospital "Virgen de la Arrixaca", University of Murcia, Murcia, Spain.
Environ Res. 2019 Nov;178:108689. doi: 10.1016/j.envres.2019.108689. Epub 2019 Aug 23.
The 5-year overall survival (OS) in childhood acute lymphoblastic leukemia (ALL) has reached 90% in high-income countries, levels that can no be longer overcome with strategies based on intensification of treatment. Other approaches in the search for new and modifiable prognostic factors are necessary to continue to improve these rates. The importance of environmental factors in the etiopathogenesis of childhood ALL has been regaining interest but its role in the prognosis and survival of this disease is not well explored. We aim to investigate the association between secondhand smoke (SHS) and survival in children diagnosed with ALL.
We analyzed survival rates in 146 patients under the age of 15 years diagnosed with ALL between January 1998 and May 2016 in the Region of Murcia, Spain. Evaluation of parental SHS and other known prognostic factors (sex, age, white blood cell count at diagnosis, cytogenetics, NCI/Rome Criteria, early response to therapy, and relapse) were assessed for impact on OS, event-free survival (EFS), cumulative incidence of relapse (CIR), and treatment-related mortality (CITRM) using Kaplan-Meier analysis, Cox regression, and Fine-Gray model.
The mean follow-up time was 105.3 months (±66.5). Prenatal exposure to SHS due to parental smoking was highly prevalent. Of the mothers, 44.4% and 55.5% of the fathers smoked at some point during pregnancy. After the child's diagnosis of ALL 39.7% of mothers and 45.9% of fathers reported smoking. The Cox proportional hazards model showed that maternal smoking during pregnancy and after diagnosis (HR = 4.396, 95% CI: 1.173-16.474, p = 0.028); and relapse (HR = 7.919; 95% CI: 2.683-21.868; p < 0.001) are independent prognostic factors in determining survival. The Fine-Gray model showed that maternal smoking during pregnancy and after diagnosis (HR = 14.525, 95% CI: 4.228-49.90, p < 0.001) is an independent prognostic factor in CITRM.
Persistent SHS worsens OS and TRM in children with ALL. This negative impact contributes to a different prognosis and may possibly provide an exceptional insight into new therapeutic approaches, including environmental aspects such as prevention and smoking cessation to improve survival outcomes.
在高收入国家，儿童急性淋巴细胞白血病（ALL）的 5 年总生存率（OS）已达到 90%，这一水平已经不能通过强化治疗策略来提高。需要寻找其他方法来寻找新的、可改变的预后因素，以继续提高这些比率。环境因素在儿童 ALL 的发病机制中的重要性重新引起了人们的兴趣，但它在这种疾病的预后和生存中的作用尚未得到很好的探索。我们旨在研究二手烟（SHS）与儿童 ALL 生存之间的关联。
我们分析了 1998 年 1 月至 2016 年 5 月期间在西班牙穆尔西亚地区年龄在 15 岁以下被诊断患有 ALL 的 146 名患者的生存率。评估父母的 SHS 以及其他已知的预后因素（性别、诊断时的白细胞计数、细胞遗传学、NCI/Rome 标准、早期治疗反应和复发）对 OS、无事件生存（EFS）、累积复发率（CIR）和治疗相关死亡率（CITRM）的影响，使用 Kaplan-Meier 分析、Cox 回归和 Fine-Gray 模型进行评估。
平均随访时间为 105.3 个月（±66.5）。产前暴露于父母吸烟引起的 SHS 非常普遍。母亲中有 44.4%，父亲中有 55.5%在怀孕期间的某个时间吸烟。在儿童被诊断患有 ALL 后，有 39.7%的母亲和 45.9%的父亲报告吸烟。Cox 比例风险模型显示，母亲在怀孕期间和诊断后吸烟（HR=4.396，95%CI：1.173-16.474，p=0.028）；以及复发（HR=7.919；95%CI：2.683-21.868；p<0.001）是决定生存的独立预后因素。Fine-Gray 模型显示，母亲在怀孕期间和诊断后吸烟（HR=14.525，95%CI：4.228-49.90，p<0.001）是 CITRM 的独立预后因素。
持续的 SHS 会降低 ALL 患儿的 OS 和 TRM。这种负面影响导致了不同的预后，并可能为新的治疗方法提供一个特殊的见解，包括环境方面，如预防和戒烟，以改善生存结果。
