Spectrum of second primary malignancies and cause-specific mortality in pediatric and adult langerhans cell histiocytosis.

With the advent of targeted therapeutics in Langerhans cell histiocytosis (LCH), there is a growing survivor population that might be at risk for late mortality from non-LCH causes, including second primary malignancies (SPMs). We undertook a large study using the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the patterns of SPMs and cause-specific mortality among individuals with LCH (2000-2016) from the US. We found an increased risk of SPMs in the cohort (standardized incidence ratio [SIR] 2.07). The pediatric group was at a high risk of developing Hodgkin lymphoma (SIR 60.93) and non-Hodgkin lymphoma (SIR 60.88). People with adult-onset LCH were found to have a high risk of developing miscellaneous malignant cancers (SIR 11.43), which primarily included myelodysplastic syndrome. Adults were also at a high risk of developing carcinoma in-situ of vulva at 2-11 months [SIR 62.72] and B-ALL at 60-119 months [SIR 66.29] after LCH diagnosis. Additionally, 5% and 1% of the patients developed prior or concomitant malignancies with LCH, respectively. The 5 yr overall survival (OS) was 96.6% for pediatric and 88.5% for adult LCH cohorts. Most common cause of death was infections in pediatric and SPMs in adult LCH. Our study highlights that despite advances in treatments, people with LCH have an increased mortality risk from non-LCH causes when compared with the general population, including a high risk of SPMs.