The type and number of disease sites, degree of organ dysfunction, and response to treatment are the main prognostic factors. Pulmonary LCH in adolescents and adults often regresses after smoking cessation.[115]Mogulkoc N, Veral A, Bishop PW, et al. Pulmonary Langerhans' cell histiocytosis; radiologic resolution following smoking cessation. Chest. 1999 May;115(5):1452-5.
http://www.ncbi.nlm.nih.gov/pubmed/10334170?tool=bestpractice.com
Age ≤3 years at presentation, hepatosplenomegaly, thrombocytopenia, polyostotic disease (≥3 bones involved), risk organ involvement, and lack of response to chemotherapy within the first 6 weeks (if risk organs are involved) are associated with increased mortality.[25]Gadner H, Grois N, Pötschger U, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62.
https://ashpublications.org/blood/article/111/5/2556/109907/Improved-outcome-in-multisystem-Langerhans-cell
http://www.ncbi.nlm.nih.gov/pubmed/18089850?tool=bestpractice.com
[26]Kilpatrick SE, Wenger DE, Gilchrist GS, et al. Langerhans' cell histiocytosis (Histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer. 1995 Dec 15;76(12):2471-84.
https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%2819951215%2976%3A12%3C2471%3A%3AAID-CNCR2820761211%3E3.0.CO%3B2-Z
http://www.ncbi.nlm.nih.gov/pubmed/8625073?tool=bestpractice.com
[116]Gadner H, Grois N, Arico M, et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34.
http://www.ncbi.nlm.nih.gov/pubmed/11343051?tool=bestpractice.com
Hepatosplenomegaly and thrombocytopenia are associated with bone marrow involvement at diagnosis, which carries a poorer prognosis.[43]McClain K, Ramsay NK, Robison L, et al. Bone marrow involvement in histiocytosis X. Med Pediatr Oncol. 1983;11(3):167-71.
http://www.ncbi.nlm.nih.gov/pubmed/6602270?tool=bestpractice.com
[44]Willis B, Ablin A, Weinberg V, et al. Disease course and late sequelae of Langerhans' cell histiocytosis: 25-year experience at the University of California, San Francisco. J Clin Oncol. 1996 Jul;14(7):2073-82.
http://www.ncbi.nlm.nih.gov/pubmed/8683239?tool=bestpractice.com
Five-year survival for patients with multisystem disease is 90% in children and 70% in adults.[11]Ribeiro KB, Degar B, Antoneli CB, et al. Ethnicity, race, and socioeconomic status influence incidence of Langerhans cell histiocytosis. Pediatr Blood Cancer. 2015 Jun;62(6):982-7.
http://www.ncbi.nlm.nih.gov/pubmed/25586293?tool=bestpractice.com
[117]Goyal G, Shah MV, Hook CC, et al. Adult disseminated Langerhans cell histiocytosis: incidence, racial disparities and long-term outcomes. Br J Haematol. 2018 Aug;182(4):579-81.
https://onlinelibrary.wiley.com/doi/10.1111/bjh.14818
http://www.ncbi.nlm.nih.gov/pubmed/28653448?tool=bestpractice.com
Patients with polyostotic disease are at higher risk of reactivation.[44]Willis B, Ablin A, Weinberg V, et al. Disease course and late sequelae of Langerhans' cell histiocytosis: 25-year experience at the University of California, San Francisco. J Clin Oncol. 1996 Jul;14(7):2073-82.
http://www.ncbi.nlm.nih.gov/pubmed/8683239?tool=bestpractice.com
Reactivation of disease with skeletal recurrence and/or new bone lesions is strongly associated with presence of diabetes insipidus in children, but not in adults.[26]Kilpatrick SE, Wenger DE, Gilchrist GS, et al. Langerhans' cell histiocytosis (Histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer. 1995 Dec 15;76(12):2471-84.
https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%2819951215%2976%3A12%3C2471%3A%3AAID-CNCR2820761211%3E3.0.CO%3B2-Z
http://www.ncbi.nlm.nih.gov/pubmed/8625073?tool=bestpractice.com
Presence of BRAF V600E mutation is associated with a 2-fold increased risk of disease reactivation.[16]Berres ML, Lim KP, Peters T, et al. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med. 2014 Apr 7;211(4):669-83.
https://rupress.org/jem/article/211/4/669/54603/BRAF-V600E-expression-in-precursor-versus
http://www.ncbi.nlm.nih.gov/pubmed/24638167?tool=bestpractice.com
In one cross-sectional study, the majority of adult survivors of childhood LCH reported long-term morbidity and adverse health-related quality of life. Hypothalamic pituitary dysfunction affected 50%, cognitive dysfunction 20%, and cerebellar symptoms 17.5%.[118]Nanduri VR, Pritchard J, Levitt G, et al. Long term morbidity and health related quality of life after multi-system Langerhans cell histiocytosis. Eur J Cancer. 2006 Oct;42(15):2563-9.
http://www.ncbi.nlm.nih.gov/pubmed/16959486?tool=bestpractice.com
Patients with LCH have often been known to experience chronic pain, fatigue, and mood disorders, which should be sought and treated.
Patients treated with BRAF inhibitors require close monitoring for the development of secondary cancers, which are associated with late mortality. These agents are established in the management of metastatic melanoma, and late sequelae of melanoma and nonmelanoma skin cancers have been reported.[119]Boussemart L, Routier E, Mateus C, et al. Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol. 2013 Jun;24(6):1691-7.
https://www.annalsofoncology.org/article/S0923-7534(19)37301-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23406731?tool=bestpractice.com