Long-term outcomes among adults with Langerhans cell histiocytosis.

Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective review of 219 adults (age ≥ 18y) with LCH. Most common presentation was multisystem (34.2%), followed by single system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (liver, spleen, or bone marrow) was seen in 8.7% cases, and 40/88 (40.2%) tested cases were BRAFV600E. At median follow-up of 74mo, 5-year progression free survival (PFS) was 58.3% and estimated median PFS was 83mo. Median overall survival (OS) was not reached; 5- and 10-year OS were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (HR 4.5) and OS (HR 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR] 2.66), specifically among <55y at diagnosis (SMR 5.94) and multisystem disease (SMR 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5y of diagnosis. After 5y, non-LCH causes of death predominated, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases. Our study highlights for the first time that adults with LCH experience early and late mortality from non-LCH causes and highlights the need for development of targeted survivorship programs to improve outcomes.