Children and adolescents with Langerhans cell histiocytosis (LCH) should be treated by a multidisciplinary team of health professionals who are experienced with this disease and its treatment. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life.
Clinical trials organized by the Histiocyte Society have been accruing patients on childhood treatment studies since the 1980s. Information on centers enrolling patients on these trials can be found on the NCI Web site.
Children with high-risk or low-risk disease should be followed annually to document and attempt to correct adverse side effects of therapy or the disease. (Refer to the Late Disease and Treatment Effects of Childhood LCH section of this summary for more information about the incidence, type, and monitoring of late effects of childhood cancer and its therapy.)
The annual incidence of LCH has been estimated to be two to ten cases per 1 million children aged 15 years or younger.[1,2] The male to female ratio (M/F) is close to one and the median age of presentation is 30 months. A report from Stockholm County, Sweden, described an annual incidence of 8.9 cases of LCH per 1 million children with a total of 29 cases in 10 years. Most of these cases were diagnosed between September and February (M/F = 1.2). A 4-year survey of 251 new LCH cases in France found an annual incidence of 4.6 cases per 1 million children younger than 15 years (M/F = 1.2). A survey of LCH in northwest England (Manchester) revealed an overall incidence of 2.6 cases per 1 million child-years.
Identical twins with LCH, and non-twin siblings or multiple cases in one family, have been reported. Over 90% of adult pulmonary LCH occurs in young adults who smoke, often more than 20 cigarettes per day.[8,9]
Although the following risk factors have been identified for LCH, strong and consistent associations have not been confirmed:
Prognosis is closely linked to the extent of disease at presentation when high-risk organs (liver, spleen, and/or bone marrow) are involved and to the response to initial treatment. The high-risk designation comes from the high mortality rate (35%) in those who did not respond well to therapy in the first 6 weeks. For many years, lung was thought to be a high-risk organ but isolated lung involvement in pediatric LCH is no longer considered to pose a significant risk of death. Because of treatment advances, the outcome for children with LCH involving high-risk organs has improved.[14,15] Data from HISTSOC-LCH-III showed an 84% overall survival (OS) rate for patients treated for 12 months with systemic chemotherapy.
Patients with single-system disease and low-risk multisystem disease do not usually die from LCH, but recurrent disease may result in considerable morbidity and significant late effects. The major treatment challenge is to reduce the 20% to 30% incidence of recurrent lesions and the significant incidence of permanent consequences in this group of patients. HISTSOC-LCH-III data showed that there was a significant difference in reactivation for risk organ subjects when comparing 6 months versus 12 months of treatment, with 12 months being better (54% vs. 37%).
Prognostic factors in LCH have been identified and can be categorized as follows:
- Age at diagnosis: Although age younger than 2 years was once thought to portend a worse prognosis, data from the LCH-II study showed that patients aged 2 years or younger without high-risk organ involvement had the same response to therapy as older patients. By contrast, the OS was poorer in neonates with risk-organ involvement compared with infants and children with the same extent of disease when patients were treated for only 6 months.
- Response to treatment: Response to therapy at 6 to 12 weeks has been shown to be a more important prognostic factor than age. The overall response to therapy is influenced by the duration and intensity of treatment.[14,15]
- Organ involvement: Involvement of craniofacial bones including orbital, mastoid, and temporal bones is associated with an increased risk of diabetes insipidus and an increased frequency of anterior pituitary hormone deficiencies and neurologic problems. (Refer to the Endocrine system subsection in the Multisystem Disease Presentation section of this summary for more information on diabetes insipidus.)
- Carstensen H, Ornvold K: The epidemiology of Langerhans cell histiocytosis in children in Denmark, 1975-89. [Abstract] Med Pediatr Oncol 21 (5): A-15, 387-8, 1993.
- Salotti JA, Nanduri V, Pearce MS, et al.: Incidence and clinical features of Langerhans cell histiocytosis in the UK and Ireland. Arch Dis Child 94 (5): 376-80, 2009. [PUBMED Abstract]
- A multicentre retrospective survey of Langerhans' cell histiocytosis: 348 cases observed between 1983 and 1993. The French Langerhans' Cell Histiocytosis Study Group. Arch Dis Child 75 (1): 17-24, 1996. [PUBMED Abstract]
- Stålemark H, Laurencikas E, Karis J, et al.: Incidence of Langerhans cell histiocytosis in children: a population-based study. Pediatr Blood Cancer 51 (1): 76-81, 2008. [PUBMED Abstract]
- Guyot-Goubin A, Donadieu J, Barkaoui M, et al.: Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000-2004. Pediatr Blood Cancer 51 (1): 71-5, 2008. [PUBMED Abstract]
- Alston RD, Tatevossian RG, McNally RJ, et al.: Incidence and survival of childhood Langerhans cell histiocytosis in Northwest England from 1954 to 1998. Pediatr Blood Cancer 48 (5): 555-60, 2007. [PUBMED Abstract]
- Aricò M, Nichols K, Whitlock JA, et al.: Familial clustering of Langerhans cell histiocytosis. Br J Haematol 107 (4): 883-8, 1999. [PUBMED Abstract]
- Tazi A, Soler P, Hance AJ: Adult pulmonary Langerhans' cell histiocytosis. Thorax 55 (5): 405-16, 2000. [PUBMED Abstract]
- Vassallo R, Ryu JH, Colby TV, et al.: Pulmonary Langerhans'-cell histiocytosis. N Engl J Med 342 (26): 1969-78, 2000. [PUBMED Abstract]
- Bhatia S, Nesbit ME Jr, Egeler RM, et al.: Epidemiologic study of Langerhans cell histiocytosis in children. J Pediatr 130 (5): 774-84, 1997. [PUBMED Abstract]
- Venkatramani R, Rosenberg S, Indramohan G, et al.: An exploratory epidemiological study of Langerhans cell histiocytosis. Pediatr Blood Cancer 59 (7): 1324-6, 2012. [PUBMED Abstract]
- Nicholson HS, Egeler RM, Nesbit ME: The epidemiology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 12 (2): 379-84, 1998. [PUBMED Abstract]
- Ronceray L, Pötschger U, Janka G, et al.: Pulmonary involvement in pediatric-onset multisystem Langerhans cell histiocytosis: effect on course and outcome. J Pediatr 161 (1): 129-33.e1-3, 2012. [PUBMED Abstract]
- Gadner H, Grois N, Arico M, et al.: A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr 138 (5): 728-34, 2001. [PUBMED Abstract]
- Gadner H, Grois N, Pötschger U, et al.: Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood 111 (5): 2556-62, 2008. [PUBMED Abstract]
- Gadner H, Minkov M, Grois N, et al.: Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood 121 (25): 5006-14, 2013. [PUBMED Abstract]
- Haupt R, Nanduri V, Calevo MG, et al.: Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatr Blood Cancer 42 (5): 438-44, 2004. [PUBMED Abstract]
- Minkov M, Prosch H, Steiner M, et al.: Langerhans cell histiocytosis in neonates. Pediatr Blood Cancer 45 (6): 802-7, 2005. [PUBMED Abstract]