Skip to main content
SpringerLink
Log in

Langerhans Cell Histiocytosis

  • Chapter
  • First Online:
Hematological Disorders in Children

  • 910 Accesses

Abstract

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by accumulation of clonal CD1a-positive immature dendritic cells (LCH cells) accompanied by infiltration of various inflammatory cells such as eosinophils, lymphocytes, macrophages, and osteoclast-like multinuclear giant cells. Mutually exclusive oncogenic mutations in genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway, such as BRAF and MAP2K1, are detected in LCH cells from more than two thirds of LCH patients, suggesting that LCH cells are neoplastic. Proinflammatory cytokines and chemokines play a role in the clinical presentation of LCH, indicating that LCH is also an inflammatory disorder. Several major issues regarding the treatment of childhood LCH remain: how do clinicians rescue patients with risk-organ involvement that do not respond to first-line therapy, and how do they reduce and treat central nervous system-related consequences such as central diabetes insipidus and neurodegeneration? More research is needed to resolve these treatment-related issues.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Guyot-Goubin A, Donadieu J, Barkaoui M, et al. Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000–2004. Pediatr Blood Cancer. 2008;51:71–5.

    Article  PubMed  Google Scholar 

  2. Horibe K, Saito AM, Takimoto T, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006–2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol. 2013;98:74–88.

    Article  PubMed  Google Scholar 

  3. Salotti JA, Nanduri V, Pearce MS, et al. Incidence and clinical features of Langerhans cell histiocytosis in the UK and Ireland. Arch Dis Child. 2009;94:376–80.

    Article  CAS  PubMed  Google Scholar 

  4. Aricò M, Girschikofsky M, Généreau T, et al. Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer. 2003;39:2341–8.

    Article  PubMed  Google Scholar 

  5. Aricò M, Danesino C. Langerhans’ cell histiocytosis: is there a role for genetics? Haematologica. 2001;86:1009–14.

    PubMed  Google Scholar 

  6. De Filippi P, Badulli C, Cuccia M, et al. Specific polymorphisms of cytokine genes are associated with different risks to develop single-system or multi-system childhood Langerhans cell histiocytosis. Br J Haematol. 2006;132:784–7.

    Article  PubMed  CAS  Google Scholar 

  7. Egeler RM, Neglia JP, Aricò M, et al. The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and other solid tumors. The LCH-Malignancy Study Group of the Histiocyte Society. Hematol Oncol Clin North Am. 1998;12:369–78.

    Article  CAS  PubMed  Google Scholar 

  8. Kato M, Seki M, Yoshida K, et al. Genomic analysis of clonal origin of Langerhans cell histiocytosis following acute lymphoblastic leukaemia. Br J Haematol. 2016;175(1):169–72.

    Article  PubMed  Google Scholar 

  9. Jaffe R, Weiss LM, Facchetti F. Tumours derived from Langerhans cells. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumours, tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008. p. 358–60.

    Google Scholar 

  10. Bains A, Parham DM. Langerhans cell histiocytosis preceding the development of juvenile xanthogranuloma: a case and review of recent developments. Pediatr Dev Pathol. 2011;14:480–4.

    Article  PubMed  Google Scholar 

  11. Kim S, Lee M, Shin HJ, et al. Coexistence of intracranial Langerhans cell histiocytosis and Erdheim-Chester disease in a pediatric patient: a case report. Childs Nerv Syst. 2016;32:893–6.

    Article  PubMed  Google Scholar 

  12. Lau SK, Chu PG, Weiss LM. Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. Am J Surg Pathol. 2008;32:615–9.

    Article  PubMed  Google Scholar 

  13. Weitzman S, Whitlock J. Uncommon histiocytic disorder: the non-Langerhans cell histiocytoses. In: Weitzman S, Egeler RM, editors. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005. p. 293–320.

    Chapter  Google Scholar 

  14. Berres ML, Merad M, Allen CE. Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X? Br J Haematol. 2015;169:3–13.

    Article  PubMed  Google Scholar 

  15. Willman CL, Busque L, Griffith BB, et al. Langerhans’-cell histiocytosis (histiocytosis X)—a clonal proliferative disease. N Engl J Med. 1994;331:154–60.

    Article  CAS  PubMed  Google Scholar 

  16. Yu RC, Chu C, Buluwela L, et al. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet. 1994;343:767–8.

    Article  CAS  PubMed  Google Scholar 

  17. Murakami I, Gogusev J, Fournet JC, et al. Detection of molecular cytogenetic aberrations in Langerhans cell histiocytosis of bone. Hum Pathol. 2002;33:555–60.

    Article  CAS  PubMed  Google Scholar 

  18. da Costa CE, Szuhai K, van Eijk R, et al. No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies. Genes Chromosomes Cancer. 2009;48:239–49.

    Article  PubMed  CAS  Google Scholar 

  19. Badalian-Very G, Vergilio JA, Degar BA, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010;116:1919–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bubolz AM, Weissinger SE, Stenzinger A, et al. Potential clinical implications of BRAF mutations in histiocytic proliferations. Oncotarget. 2014;5:4060–70.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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;211:669–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Brown NA, Furtado LV, Betz BL, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood. 2014;124:1655–8.

    Article  CAS  PubMed  Google Scholar 

  23. Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124:3007–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nelson DS, Quispel W, Badalian-Very G, et al. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood. 2014;123:3152–5.

    Article  CAS  PubMed  Google Scholar 

  25. Nelson DS, van Halteren A, Quispel WT, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer. 2015;54:361–8.

    Article  CAS  PubMed  Google Scholar 

  26. Allen CE, Li L, Peters TL, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol. 2010;184:4557–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Geissmann F, Geissmann F, Lepelletier Y, et al. Differentiation of Langerhans cells in Langerhans cell histiocytosis. Blood. 2001;97:1241–8.

    Article  CAS  PubMed  Google Scholar 

  28. Hutter C, Kauer M, Simonitsch-Klupp I, et al. Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells. Blood. 2012;120:5199–208.

    Article  CAS  PubMed  Google Scholar 

  29. Rodig SJ, Payne EG, Degar BA, et al. Aggressive Langerhans cell histiocytosis following T-ALL: clonally related neoplasms with persistent expression of constitutively active NOTCH1. Am J Hematol. 2008;83:116–21.

    Article  CAS  PubMed  Google Scholar 

  30. Yokokawa Y, Taki T, Chinen Y, et al. Unique clonal relationship between T-cell acute lymphoblastic leukemia and subsequent Langerhans cell histiocytosis with TCR rearrangement and NOTCH1 mutation. Genes Chromosomes Cancer. 2015;54:409–17.

    Article  CAS  PubMed  Google Scholar 

  31. Senechal B, Elain G, Jeziorski E, et al. Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. PLoS Med. 2007;4:e253.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Annels NE, Annels NE, Da Costa CE, et al. Aberrant chemokine receptor expression and chemokine production by Langerhans cells underlies the pathogenesis of Langerhans cell histiocytosis. J Exp Med. 2003;197:1385–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Egeler RM, Favara BE, van Meurs M, et al. Differential in situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: abundant expression of cytokines relevant to disease and treatment. Blood. 1999;94:4195–201.

    CAS  PubMed  Google Scholar 

  34. Egeler RM, Favara BE, Laman JD, et al. Abundant expression of CD40 and CD40-ligand (CD154) in paediatric Langerhans cell histiocytosis lesions. Eur J Cancer. 2000;36:2105–10.

    Article  CAS  PubMed  Google Scholar 

  35. Uede T. Osteopontin, intrinsic tissue regulator of intractable inflammatory diseases. Pathol Int. 2011;61:265–80.

    Article  CAS  PubMed  Google Scholar 

  36. Morimoto A, Nakamura S, Shioda Y et al. Comprehensive analysis of serum cytokine/chemokine and growth factors in pediatric patients with Langerhans cell histiocytosis. Pediatr Blood Cancer 2011a;56:696 [abstract].

    Google Scholar 

  37. Ikawa Y, Nishimura R, Araki R, et al. Pathognomonic serum cytokine profiles identify life-threatening Langerhans cell histiocytosis. Br J Haematol. 2017;176(3):495–7.

    Article  PubMed  Google Scholar 

  38. Oh Y, Morimoto A, Shioda Y, et al. High serum osteopontin levels in pediatric patients with high risk Langerhans cell histiocytosis. Cytokine. 2014a;70:194–7.

    Article  CAS  PubMed  Google Scholar 

  39. da Costa CE, Annels NE, Faaij CM, et al. Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. J Exp Med. 2005;201:687–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Ishii R, Morimoto A, Ikushima S, et al. High serum values of soluble CD154, IL-2 receptor, RANKL and osteoprotegerin in Langerhans cell histiocytosis. Pediatr Blood Cancer. 2006;47:194–9.

    Article  PubMed  Google Scholar 

  41. Coury F, Annels N, Rivollier A, et al. Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion. Nat Med. 2008;14:81–7.

    Article  CAS  PubMed  Google Scholar 

  42. Murakami I, Morimoto A, Oka T, et al. IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy. Virchows Arch. 2013;462:219–28.

    Article  CAS  PubMed  Google Scholar 

  43. Oh Y, Oh I, Morimoto J, et al. Osteopontin has a crucial role in osteoclast-like multinucleated giant cell formation. J Cell Biochem. 2014b;115:585–95.

    Article  CAS  PubMed  Google Scholar 

  44. Murakami I, Matsushita M, Iwasaki T, et al. Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis. Hum Pathol. 2014;45:119–26.

    Article  CAS  PubMed  Google Scholar 

  45. Murakami I, Matsushita M, Iwasaki T, et al. Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis. Cell Commun Signal. 2015a;13:13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Prasse A, Stahl M, Schulz G, et al. Essential role of osteopontin in smoking-related interstitial lung diseases. Am J Pathol. 2009;174:1683–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Morimoto A, Ishida Y, Suzuki N, et al. Nationwide survey of single-system single site LCH in Japan. Pediatr Blood Cancer. 2010;54:98–102.

    Article  PubMed  Google Scholar 

  48. Weitzman S, Egeler RM. Langerhans cell histiocytosis of bone. In: Weitzman S, Egeler RM, editors. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005. p. 154–73.

    Chapter  Google Scholar 

  49. Imashuku S, Kinugawa N, Matsuzaki A, et al. Langerhans cell histiocytosis with multifocal bone lesions: comparative clinical features between single and multi-systems. Int J Hematol. 2009;90:506–12.

    Article  PubMed  Google Scholar 

  50. Phillips M, Allen C, Gerson P, et al. Comparison of FDG-PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis. Pediatr Blood Cancer. 2009;52:97–101.

    Article  PubMed  Google Scholar 

  51. Goo HW, Yang DH, Ra YS, et al. Whole-body MRI of Langerhans cell histiocytosis: comparison with radiography and bone scintigraphy. Pediatr Radiol. 2006;36:1019–31.

    Article  PubMed  Google Scholar 

  52. Aricò M, Astigarraga I, Braier J, et al. Lack of bone lesions at diagnosis is associated with inferior outcome in multisystem Langerhans cell histiocytosis of childhood. Br J Haematol. 2015;169:241–8.

    Article  PubMed  CAS  Google Scholar 

  53. Krafchik B, Pope E, Walsh S. Histiocytosis of the skin in children and adults. In: Weitzman S, Egeler RM, editors. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005. p. 130–53.

    Google Scholar 

  54. Simko SJ, Garmezy B, Abhyankar H, et al. Differentiating skin-limited and multisystem Langerhans cell histiocytosis. J Pediatr. 2014a;165:990–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Battistella M, Fraitag S, Teillac DH, et al. Neonatal and early infantile cutaneous Langerhans cell histiocytosis: comparison of self-regressive and non-self-regressive forms. Arch Dermatol. 2010;146:149–56.

    Article  PubMed  Google Scholar 

  56. Minkov M, Prosch H, Steiner M, et al. Langerhans cell histiocytosis in neonates. Pediatr Blood Cancer. 2005;45:802–7.

    Article  CAS  PubMed  Google Scholar 

  57. Lau L, Krafchik B, Trebo MM, et al. Cutaneous Langerhans cell histiocytosis in children under one year. Pediatr Blood Cancer. 2006;46:66–71.

    Article  PubMed  Google Scholar 

  58. Morimoto A, Shioda Y, Imamura T, et al. Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study. Int J Hematol. 2016;104:99–109.

    Article  CAS  PubMed  Google Scholar 

  59. Ronceray L, Pötschger U, Janka G, et al. Pulmonary involvement in pediatric-onset multisystem Langerhans cell histiocytosis: effect on course and outcome. J Pediatr. 2012;161:129-33.e1–3.

    Article  Google Scholar 

  60. Haupt R, Minkov M, Astigarraga I, et al. Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer. 2013;60:175–84.

    Article  PubMed  Google Scholar 

  61. Braier JL, Rosso D, Latella A, et al. Importance of multi-lineage hematologic involvement and hypoalbuminemia at diagnosis in patients with “risk-organ” multi-system Langerhans cell histiocytosis. J Pediatr Hematol Oncol. 2010;32:e122–5.

    Article  PubMed  Google Scholar 

  62. Braier J, Ciocca M, Latella A, et al. Cholestasis, sclerosing cholangitis, and liver transplantation in Langerhans cell histiocytosis. Med Pediatr Oncol. 2002;38:178–82.

    Article  PubMed  Google Scholar 

  63. Matsubayashi T, Miwa Y, Saito I, et al. KL-6: marker for pulmonary involvement in Langerhans cell histiocytosis in infants. J Pediatr Hematol Oncol. 2004;26:584–6.

    Article  PubMed  Google Scholar 

  64. Dauriat G, Mal H, Thabut G, et al. Lung transplantation for pulmonary Langerhans’ cell histiocytosis: a multicenter analysis. Transplantation. 2006;81:746–50.

    Article  PubMed  Google Scholar 

  65. Grois N, Fahrner B, Arceci RJ, et al. Central nervous system disease in Langerhans cell histiocytosis. J Pediatr. 2010;156:873–81.

    Article  PubMed  Google Scholar 

  66. Dhall G, Finlay JL, Dunkel IJ, et al. Analysis of outcome for patients with mass lesions of the central nervous system due to Langerhans cell histiocytosis treated with 2-chlorodeoxyadenosine. Pediatr Blood Cancer. 2008;50:72–9.

    Article  PubMed  Google Scholar 

  67. Shioda Y, Adachi S, Imashuku S, et al. Analysis of 43 cases of Langerhans cell histiocytosis (LCH)-induced central diabetes insipidus registered in the JLSG-96 and JLSG-02 studies in Japan. Int J Hematol. 2011;94:545–51.

    Article  CAS  PubMed  Google Scholar 

  68. Grois N, Potschger U, Prosch H, et al. Risk factors for diabetes insipidus in Langerhans cell histiocytosis. Pediatr Blood Cancer. 2006;46:228–33.

    Article  CAS  PubMed  Google Scholar 

  69. Donadieu J, Rolon MA, Thomas C, et al. Endocrine involvement in pediatric-onset Langerhans’ cell histiocytosis: a population-based study. J Pediatr. 2004;144:344–50.

    Article  PubMed  Google Scholar 

  70. Grois N, Prayer D, Prosch H, et al. Course and clinical impact of magnetic resonance imaging findings in diabetes insipidus associated with Langerhans cell histiocytosis. Pediatr Blood Cancer. 2004;43:59–65.

    Article  PubMed  Google Scholar 

  71. Imashuku S, Kudo N, Kaneda S, et al. Treatment of patients with hypothalamic-pituitary lesions as adult-onset Langerhans cell histiocytosis. Int J Hematol. 2011;94:556–60.

    Article  PubMed  Google Scholar 

  72. Imashuku S, Ishida S, Koike K, et al. Cerebellar ataxia in pediatric patients with Langerhans cell histiocytosis. J Pediatr Hematol Oncol. 2004;26:735–9.

    Article  PubMed  Google Scholar 

  73. Wnorowski M, Prosch H, Prayer D, et al. Pattern and course of neurodegeneration in Langerhans cell histiocytosis. J Pediatr. 2008;153:127–32.

    Article  PubMed  Google Scholar 

  74. Prosch H, Grois N, Wnorowski M, et al. Long-term MR imaging course of neurodegenerative Langerhans cell histiocytosis. Am J Neuroradiol. 2007;28:1022–8.

    Article  CAS  PubMed  Google Scholar 

  75. Grois N, Prayer D, Prosch H, et al. Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain. 2005;128(Pt 4):829–38.

    Article  PubMed  Google Scholar 

  76. Imashuku S, Shioda Y, Kobayashi R, et al. Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Japan LCH Study Group. Haematologica. 2008;93:615–8.

    Article  PubMed  Google Scholar 

  77. Imashuku S, Fujita N, Shioda Y, et al. Follow-up of pediatric patients treated by IVIG for Langerhans cell histiocytosis (LCH)-related neurodegenerative CNS disease. Int J Hematol. 2015;101:191–7.

    Article  PubMed  Google Scholar 

  78. Imashuku S, Shioda Y, Tsunematsu Y. VCR/AraC chemotherapy and ND-CNS-LCH. Pediatr Blood Cancer. 2010;55:215–6.

    PubMed  Google Scholar 

  79. Ehrhardt MJ, Karst J, Donohoue PA, et al. Recognition and treatment of concurrent active and neurodegenerative Langerhans cell histiocytosis: a case report. J Pediatr Hematol Oncol. 2015;37:e37–40.

    Article  PubMed  Google Scholar 

  80. Edelweiss M, Medeiros LJ, Suster S, et al. Lymph node involvement by Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical study of 20 cases. Hum Pathol. 2007;38:1463–9.

    Article  CAS  PubMed  Google Scholar 

  81. Ducassou S, Seyrig F, Thomas C, et al. Thymus and mediastinal node involvement in childhood Langerhans cell histiocytosis: long-term follow-up from the French National Cohort. Pediatr Blood Cancer. 2013;60:1759–65.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Madrigal-Martínez-Pereda C, Guerrero-Rodríguez V, Guisado-Moya B, et al. Langerhans cell histiocytosis: literature review and descriptive analysis of oral manifestations. Med Oral Patol Oral Cir Bucal. 2009;14:E222–8.

    PubMed  Google Scholar 

  83. Yadav SP, Kharya G, Mohan N, et al. A. Langerhans cell histiocytosis with digestive tract involvement. Pediatr Blood Cancer. 2010;55:748–53.

    Article  PubMed  Google Scholar 

  84. Shima H, Takahashi T, Shimada H. Protein-losing enteropathy caused by gastrointestinal tract-involved Langerhans cell histiocytosis. Pediatrics. 2010;125:e426–32.

    Article  PubMed  Google Scholar 

  85. Burnett A, Carney D, Mukhopadhyay S, et al. Thyroid involvement with Langerhans cell histiocytosis in a 3-year-old male. Pediatr Blood Cancer. 2008;50:726–7.

    Article  PubMed  Google Scholar 

  86. Goyal R, Das A, Nijhawan R, et al. Langerhans cell histiocytosis infiltration into pancreas and kidney. Pediatr Blood Cancer. 2007;49:748–50.

    Article  PubMed  Google Scholar 

  87. Hyman DM, Diamond EL, Vibat CR, et al. Prospective blinded study of BRAFV600E mutation detection in cell-free DNA of patients with systemic histiocytic disorders. Cancer Discov. 2015;5:64–71.

    Article  CAS  PubMed  Google Scholar 

  88. Kobayashi M, Tojo A. The BRAF-V600E mutation in circulating cell-free DNA is a promising biomarker of high-risk adult Langerhans cell histiocytosis. Blood. 2014;124:2610–1.

    Article  CAS  PubMed  Google Scholar 

  89. Murakami I, Oh Y, Morimoto A, et al. Acute-phase ITIH4 levels distinguish multi-system from single-system Langerhans cell histiocytosis via plasma peptidomics. Clin Proteomics. 2015b;12:16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Donadieu J, Egeler RM, Pritchard J. Langerhans cell histiocytosis: a clinical update. In: Weitzman S, Egeler RM, editors. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005. p. 95–129.

    Google Scholar 

  91. Gadner H, Grois N, Arico M, et al. A randomized trial of treatment for multisystem Langerhans’ cell histiocytosis. J Pediatr. 2001;138:728–34.

    Article  CAS  PubMed  Google Scholar 

  92. Kudo K, Yoshida H, Kiyoi H, et al. Etoposide-related acute promyelocytic leukemia. Leukemia. 1998;12:1171–5.

    Article  CAS  PubMed  Google Scholar 

  93. Haupt R, Nanduri V, Egeler RM. Late effects of Langerhans cell histiocytosis and its association with malignancy. In: Weitzman S, Egeler RM, editors. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005. p. 272–92.

    Google Scholar 

  94. Egeler RM, Thompson Jr RC, Voûte PA, et al. Intralesional infiltration of corticosteroids in localized Langerhans’ cell histiocytosis. J Pediatr Orthop. 1992;12:811–4.

    Article  CAS  PubMed  Google Scholar 

  95. Minkov M, Grois N, McClain K et al. Standard of care LCH treatment guidelines. 2009. http://www.histiocytesociety.org/document.doc?id=290. Accessed 10 Jun 2016.

  96. Gadner H, Grois N, Pötschger U, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008;111:2556–62.

    Article  CAS  PubMed  Google Scholar 

  97. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121:5006–14.

    Article  CAS  PubMed  Google Scholar 

  98. Morimoto A, Ikushima S, Kinugawa N, et al. Improved outcome in the treatment of pediatric multifocal Langerhans cell histiocytosis: results from the Japan Langerhans Cell Histiocytosis Study Group-96 protocol study. Cancer. 2006;107:613–9.

    Article  PubMed  Google Scholar 

  99. Minkov M, Grois N, Heitger A, et al. Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Med Pediatr Oncol. 2002;39:581–5.

    Article  PubMed  Google Scholar 

  100. Donadieu J, Bernard F, van Noesel M, et al. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015;126:1415–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Simko SJ, Tran HD, Jones J, et al. Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease. Pediatr Blood Cancer. 2014b;61:479–87.

    Article  CAS  PubMed  Google Scholar 

  102. Rosso DA, Amaral D, Latella A, et al. Reduced doses of cladribine and cytarabine regimen was effective and well tolerated in patients with refractory-risk multisystem Langerhans cell histiocytosis. Br J Haematol. 2016;172:287–90.

    Article  PubMed  Google Scholar 

  103. Kudo K, Ohga S, Morimoto A, et al. Improved outcome of refractory Langerhans cell histiocytosis in children with hematopoietic stem cell transplantation in Japan. Bone Marrow Transplant. 2010;45:901–6.

    Article  CAS  PubMed  Google Scholar 

  104. Veys PA, Nanduri V, Baker KS, et al. Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning. Br J Haematol. 2015;169:711–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Steiner M, Matthes-Martin S, Attarbaschi A, et al. Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant. 2005;36:215–25.

    Article  CAS  PubMed  Google Scholar 

  106. Héritier S, Jehanne M, Leverger G, et al. Vemurafenib use in an infant for high-risk Langerhans cell histiocytosis. JAMA Oncol. 2015;1:836–8.

    Article  PubMed  Google Scholar 

  107. Minkov M, Steiner M, Pötschger U, et al. Reactivations in multisystem Langerhans cell histiocytosis: data of the international LCH registry. J Pediatr. 2008;153(5):700.

    Article  PubMed  Google Scholar 

  108. Morimoto A, Kobayashi R, Maeda M, et al. Impact of reactivation on the sequelae of multi-system Langerhans cell histiocytosis patients. Pediatr Blood Cancer. 2008;50:931–2.

    Article  PubMed  Google Scholar 

  109. Morimoto A, Shioda Y, Imamura T, et al. Nationwide survey of bisphosphonate therapy for children with reactivated Langerhans cell histiocytosis in Japan. Pediatr Blood Cancer. 2011b;56:110–5.

    Article  PubMed  Google Scholar 

  110. Imamura T, Sato T, Shiota Y, et al. Outcome of pediatric patients with Langerhans cell histiocytosis treated with 2 chlorodeoxyadenosine: a nationwide survey in Japan. Int J Hematol. 2010;91:646–51.

    Article  CAS  PubMed  Google Scholar 

  111. Weitzman S, Braier J, Donadieu J, et al. 2′-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). Results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009;53:1271–6.

    Article  PubMed  Google Scholar 

  112. Suzuki D, Kobayashi R, Sano H, et al. Spontaneous remission of 2-chlorodeoxyadenosine (2-CdA)-related secondary myelodysplastic syndrome in a patient with refractory Langerhans cell histiocytosis. Int J Hematol. 2013;97:782–5.

    Article  PubMed  Google Scholar 

  113. Yamada K, Yasui M, Sawada A, et al. Severe persistent bone marrow failure following therapy with 2-chlorodeoxyadenosine for relapsing juvenile xanthogranuloma of the brain. Pediatr Blood Cancer. 2012;58(2):300.

    Article  PubMed  Google Scholar 

  114. 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. 2004;42:438–44.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Jichi Medical University of Medicine, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Akira Morimoto

Authors
  1. Akira Morimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akira Morimoto .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan

    Eiichi Ishii

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Morimoto, A. (2017). Langerhans Cell Histiocytosis. In: Ishii, E. (eds) Hematological Disorders in Children. Springer, Singapore. https://doi.org/10.1007/978-981-10-3886-0_11

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-3886-0_11

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-3885-3

  • Online ISBN: 978-981-10-3886-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation