Secondhand smoke: A new and modifiable prognostic factor in childhood acute lymphoblastic leukemias

Background: 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. Methods: 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. Results: 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. Conclusions: 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.