An overview of the treatment of Langerhans cell histiocytosis in adult patients

Czech version

Authors: Z. Adam; M. Krejčí; L. Pour; P. Szturz; R. Hájek
Authors‘ workplace: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Mayer, CSc.
Published in: Vnitř Lék 2010; 56(Supplementum 2): 131-140
Category: Langerhans cell histiocytosis and some other Hematology rare diseases

Overview

Treatment of Langerhans cell histiocytosis (LCH) is determined by the stage of the disease. The treatment of choice in a localized form of the disease is a surgery or local application of glucocorticoids. If skin only is affected: local glukocorticoids or tacrolimus, and, should this treatment be unsuccessful, systemic treatment with methotrexate or thalidomide or short-term PUVA therapy. A combined treatment with vinblastin and mercaptopurin with prednisone represents the first line treatment in patients with generalized disease; in case of the lack of efficacy of treatment involving vinblastin or in the case of initial treatment of aggressive forms, cladribine might be used as the first line treatment. Other cytostatics or, alternatively, high-dose chemotherapy with autologous or allogeneic transplantation may be used if this treatment is unsuccessful. Anecdotal evidence also suggests efficacy of other treatment modalities (anti-TNF, retinoids, cyclooxygenase, inhibitors, interferon α, imatinib) although this has not been proven in clinical studies. Bisphosphonates have been shown to be effective in patients with bone involvement.

Key words:
Langerhans cell histiocytosis – vinblastine – thalidomide – cladribine – bisphosphonate

Sources

1. Broadbent V, Gadner H. Current therapy for Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998; 12: 327–338.

2. Vassallo R, Ryu JH, Schroeder DE et al. Clinical outcomes of pulmonary Langerhans’ cell histiocytosis in adults. N Engl J Med 2002; 346: 484–490.

3. Nezelof C, Basset F. Langerhans cell histioctosis research. Past, present and future. Hematol Oncol Clin North Am 1998; 12: 385–406.

4. Shima H, Takahashi T, Shimada H. Protein-losing enteropathy caused by gastrointestinal tract-involved Langerhans cell histiocytosis. Pediatrics 2010; 125: e426–e432.

5. Wang X, Yang S, Tu P et al. A case of Langerhans cell histiocytosis in an adult with initial symptoms confined to the skin. Int J Dermatol 2010; 49: 337–339.

6. Grois N, Fahrner B, Arceci RJ et al. Histiocyte Society CNS LCH Study Group. Central nervous system disease in Langerhans cell histiocytosis. J Pediatr 2010; 156: 873–881.

7. Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: Current concepts and treatments. Cancer Treat Rev 2010; 36: 354–356.

8. Fichter J, Doberauer C, Seegenschmiedt H. Langerhans cell histiocytosis in adults: An interdisciplinary challenge. Dtsch Artebl 2007; 104: 2347–2353.

9. Gadner H, Heitger A, Grois N et al. Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group. Med Pediatr Oncol 1994; 23: 72–80.

10. Malpas JS. Langerhans cell histiocytosis in adults. Hematol Oncol Clin North Am 1998; 12: 259–268.

11. Stockschlaeder M, Sucker C. Adult Langerhans cell histiocytosis group. Eur J Haematol 2006; 76: 363–368.

12. Bernstrand C, Björk O, Ahnström L et al. Intralesional steroids in Langerhans cell histiocytosis of bone. Acta Paediatr 1996; 85: 502–504.

13. Egeler MR, Thompson RC Jr, Voûte PA et al. Intralesional infiltration of corticosteroids in localized Langerhans’ cell histiocytosis. J Pediatr Orthop 1992; 12: 811–814.

14. Nebelung W, Röpke M, Kluba U et al. Treatment concepts in osseous manifestations of Langerhans cell histiocytosis. Z Orthop Ihre Grenzgeb 1999; 137: 236–243.

15. Putters TF, deVisscher JG, van Veen A et al. Intralesional infiltration of corticosteroids in the treatment of localised Langerhans’ cell histiocytosis of the mandibule. Int J Oral Maxillofac Surg 2005; 34: 571–575.

16. Alexiou GA, Prodromou N. Treatment options for localized Langerhans cell histiocytosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 801–802.

17. Esen A, Dolanmaz D, Kalayci A et al. Treatment of localized Langerhans’ cell histiocytosis of the mandible with intralesional steroid injection: report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: e53–e58.

18. Dornfeld S, Winkler C, Dörr W et al. Stralentherapie bei Histiocytosis X. Strahlenther Onkol 1998; 174: 534–535.

19. Cassady JR. Current role of radiation therapy in the management of histiocytosis X. Hematol Oncol Clin North Am 1987; 1: 123–129.

20. Gadner H, Ladisch S. The treatment of Langerhans cell histiocytosis. In: Weitzman S, Egeler RM (eds). Histiocytic disorders of children and adults. Cambridge: Cambridge University Press 2005: 229–253.

21. Olschewski T, Seegenschmiedt MH. Radiotherapy of Langerhans’ cell histiocytosis: Results and implication of a National Patterns-of-Care Study. Strahlenther Oncol 2006; 182: 629–634.

22. Krafchik B, Pope E, Walsh SR. Histiocytosis of the skin. In: Weitzman S, Egeler RM (eds). Histiocytic disorders of children and adults. Cambridge: Cambridge University Press 2005: 130–153.

23. O’Kane D, Jenkinson H, Carson J. Langerhans cell histiocytosis associated with breast carcinoma successfully treated with topical imiquimod. Clin Exp Dermatol 2009; 34: e829–e832.

24. Lonsdale-Eccles AA, Haworth AE, McCrae FC et al. Successful treatment of multicentric reticulohistiocytosis with leflunomide. Br J Dermatol 2009; 161: 470–472.

25. Rosén K, Jontell M, Mobacken H et al. Epidermal Langerhans’ cells in chronic eczematous dermatitis of the palms treated with PUVA and UVB. Acta Derm Venereol 1989; 69: 200–205.

26. Kwon OS, CHo KH, Song KY. Primary cutaneous Langerhans cell histiocytosis treated with photochemotherapy. J Dermatol 1997; 24: 54–56.

27. Hoeger PH, Nanduri VR, Harper JI et al. Long term follow up of topical mustine treatment for cutaneous Langerhans cell histiocytosis. Arch Dis Child 2000; 82: 483–487.

28. Do JE, Lee JY, Kim YC. Successful treatment of cutaneous Langerhans’ cell histiocytosis with targeted narrowband ultraviolet B phototherapy in an infant. Clin Exp Dermatol 2009; 34: e280–e281.

29. Montero AJ, Díaz-Montero CM, Malpica A et al. Langerhans cell histiocytosis of the female genital tract: a literature review. Int J Gynecol Cancer 2003; 13: 381–388.

30. Titgemeyer C, Grois N, Minkov M et al. Pattern and course of single system disease in Langerhans cell histiocytytosis data from the DAL-HX 83- and 90-study. Med Pediatr Oncol 2001; 37: 108–114.

31. Helmbold P, Hegemann B, Holzhausen HJ et al. Low dose oral etoposide monotherapy in adult Langerhans cell histiocytosis. Arch Dermatol 1998; 134: 1275–1278.

32. Abla O, Weitzman S, Minkov M et al. Diabetes insipidus in Langerhans cell histiocytosis: When is treatment indicated? Pediatr Blood Cancer 2009; 52: 555–556.

33. Grois N, Flucher-Wolfram B, Heitger Aet al. Diabetes insipidus in Langerhans cell histiocytosis: result from the DAL-HX 83 study. Med Pediatr Oncol 1995; 24: 248–256.

34. Gadner H, Grois N, Arico M et al. A randomized trial of treatment of multisystem Langerhans’ cell histiocytosis. J Pediatr 2001; 138: 728–734.

35. Tazi A. Adult Langerhans cell histiocytosis. Eur Respir J 2006; 27: 1272–1285.

36. Pruvost C, Picard-Dahan C, Bonnefond B et al. Vinblastine treatment for extensive non-X histiocytosis (xanthoma disseminatum). Ann Dermatol Venereol 2004; 131: 271–273.

37. Broadbent V, Pritchard J, Yeomans E. Etoposide (VP16) in the treatment of multisystem Langerhans cell hitocytosis (histiocytosis X). Med Pediatr Oncol 1989; 17: 97–100.

38. Gadner H, Grois N, Arico M et al. A randomized trial of treatment for multisystem Langerhans cell histiocytosis. J Pediatr 2001; 138: 728–734.

39. Gadner H, Grois N, Pötschger U et al. Improvement outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood 2008; 111: 2556–2562.

40. Ladisch S, Gadner H, Aricò M et al. LCH-1: A randomized trial of etoposide vs. vinblastine in disseminated Langerhans cell histiocytosis. The Histiocyte Society. Med Pediatr Oncol 1994; 23: 107–110.

41. Mottl H, Koutecký J, Ganevová M. Strategie léčby histiocytózy z Langerhansových buněk u dětí. Čes Slov Pediat 1994; 49: 81.

42. Tsele E, Thomas M, Chu AC. Treatment of adult Langerhans cell histiocytosis with etoposide. J Am Acad Dermatol 1992; 27: 61–64.

43. Minkov M, Grois N, Heitger A et al. Treatment of multisystem Langerhans cell histiocytosis. Results of the DAL-HX 83 and DAL-HX 90 studies. DAL-HX Study Group. Klin Pediatr 2000; 212: 139–144.

44. Minkov M, Grois N, Heitger A et al. Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic factor. Med Pediatr Oncol 2002; 39: 581–585.

45. Arceci RJ, Brenner MK, Pritchard J et al. Controversies and new approaches to treatment of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998; 12: 339–357.

46. Jones B, Kung F, Chevalier L et al. Chemotherapy of reticuloendotheliosis. Comparison of methotrexate plus prednisone vs. vincristine plus prednisone. Cancer 1974; 34: 1011–1017.

47. McClain KL. Drug therapy for the treatment of Langerhans cell histiocytosis. Expert Opin Pharmacother 2005; 6: 2435–2441.

48. Egeler RM, Kraker J, Voûte PA. Cytosine-arabinoside, vincristine and prednisone in the treatment of children with disseminated Langerhans cell histiocytosis with organ dysfunction: experience at a single institution. Med Pediatr Oncol 1993; 21: 265–270.

49. Carroll C, Collier A, Malempati S et al. Intermediate dose methotrexate for recurrent Langerhans cell histiocytosis. In: Proceedings of the 24th annual meeting of the histiocyte society. Berlin: Germany 2008.

50. Saven A, Burian C. Cladribine activity in adult Langerhans cell histiocytosis. Blood 1999; 93: 4125–4130.

51. Aricò M, Colella R, Conter V et al. Cyclosporine therapy for refractory Langerhans cell histiocytosis. Med Pediatr Oncol 1995; 25: 12–16.

52. Minkov M, Grois N, Braier J et al. Immunosuppressive treatment for chemotherapy-resistant multisystem Langerhans cell histiocytosis. Med Pediatr Oncol 2003; 40: 253–256.

53. Minkov M, Grois N, Broadbent V et al. Cyclosporine A therapy for multisystem Langerhans cell histiocytosis. Med Pediatr Oncol 1999; 33: 482–485.

54. Bellmunt J, Albanell J, Salud A et al. Interferon and disseminated Langerhans cell histiocytosis. Med Pediatr Oncol 1992; 20: 336–337.

55. Culić S, Jakobson A, Culić V et al. Etoposide as the basis and interferon-alpha as the maintenance therapy for Langerhans cell histiocytosis. Pediatr Hematol Oncol 2001; 18: 291–294.

56. Esmaeli B, Ahmadi A, Tang R et al. Interferon therapy for orbital infiltration secondary to Erdheim-Chester disease. Am J Ophthalmol 2001; 132: 945–947.

57. Sato Y, Ikeda Y, Ito E et al. Histiocytosis X: successful treatment with recombinant interferon alpha-2a. Acta Paediatr Jpn 1990; 32: 151–154.

58. Takemori H, Sakata Y, Suzuki H et al. A case of malignant histiocytosis successfully treated with combination of interferon alpha and etoposide therapy. Jpn J Clin Oncol 1990; 20: 431–435.

59. Brown RE. Interferon-alpha therapy protein kinase C alpha and Langerhans cell histiocytosis. Med Pediatr Oncol 2003; 41: 63–64.

60. Dina A, Zahava V, Iness M. The role of vascular endothelial growth factor in Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2005; 27: 62–66.

61. Reichle A, Vogt T, Kunz-Schughart L et al. Anti-inflammatory and angiostatic therapy in chemorefractory multisystem Langerhans’ cell histiocytosis of adults. Br J Haematol 2005; 128: 730–732.

62. Andersson By U, Tani E, Andersson U et al. Tumor necrosis factor, interleukin 11, and leukemia inhibitory factor produced by Langerhans cells in Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2004; 26: 706–711.

63. Aouba A, De Bandt M, Aslangul E et al. Haemophagocytic syndrome in a rheumatoid arthritis patient treated with infliximab. Rheumatology (Oxford) 2003; 42: 800–802.

64. Henter JI, Karlén J, Calming U et al. Successful treatment of Langerhans’-cell histiocytosis with etanercept. N Engl J Med 2001; 345: 1577–1578.

65. 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: 194–199.

66. Kalajian AH, Callen JP. Multicentric reticulohistiocytosis successfully treated with infliximab: an illustrative case and evaluation of cytokine expression supporting anti-tumor necrosis factor therapy. Arch Dermatol 2008; 144: 1360–1366.

67. Kovach BT, Calamia KT, Walsh JS et al. Treatment of multicentric reticulohistiocytosis with etanercept. Arch Dermatol 2004; 140: 919–921.

68. Lee MW, Lee EY, Jeong YI et al. Successful treatment of multicentric reticulohistiocytosis with a combination of infliximab, prednisolone and methotrexate. Acta Derm Venereol 2004; 84: 478–479.

69. Lovelace K, Loyd A, Adelson D et al. Etanercept and the treatment of multicentric reticulohistiocytosis. Arch Dermatol 2005; 141: 1167–1168.

70. Rodríguez HN, García I, Alba A et al. Infliximab-induced reactivated Langerhan’s cell histiocytosis in a patient with ulcerative colitis. Inflamm Bowel Dis 2009; 15: 1286–1287.

71. Sellam J, Deslandre CJ, Dubreuil F et al. Refractory multicentric reticulohistiocytosis treated by infliximab: two cases. Clin Exp Rheumatol 2005; 23: 97–99.

72. Shannon SE, Schumacher HR, Self S et al. Multicentric reticulohistiocytosis responding to tumor necrosis factor-alpha inhibition in a renal transplant patient. J Rheumatol 2005; 32: 565–567.

73. Aouba A, Georgin-Lavialle S, Pagnoux C et al. Rationale and efficacy of interleukin-1 targeting in Erdheim-Chester disease. Blood 2010; Epub ahead of print.

74. Alioua Z, Hjira N, Oumakhir S et al. Thalidomide in adult multisystem Langerhans cell histiocytosis: a case report. Rev Med Interne 2006; 27: 633–636.

75. Bensaid P, Machet L, Vaillant L et al. Langerhans-cell histiocytosis in the adult: regressive parotid involvement following thalidomide therapy. Ann Dermatol Venereol 1992; 119: 281–283.

76. Bertolini F, Mingrone W, Alietti A et al. Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. Analysis of clinical results and of surrogate angiogenesis markers. Ann Oncol 2001; 12: 987–990.

77. Broekaert SM, Metzler G, Burgdorf Wet al. Multisystem Langerhans cell histiocytosis: successful treatment with thalidomide. Am J Clin Dermatol 2007; 8: 311–314.

78. Chen M, Doherty SD, Hsu S. Innovative uses of thalidomide. Dermatol Clin 2010; 28: 577–586.

79. Claudon A, Dietemann JL, Hamman R et al. Interest in thalidomide in cutaneo-mucous and hypothalamo-hypophyseal involvement of Langerhans cell histiocytosis. Rev Med Interne 2002; 23: 651–656.

80. Kolde G, Schulze P, Sterry W. Mixed response to thalidomide therapy in adults: two cases of multisystem Langerhans’ cell histiocytosis. Acta Derm Venereol 2002; 82: 384–386.

81. Lair G, Marie I, Cailleux N et al. Langerhans histiocytosis in adults: cutaneous and mucous lesion regression after treatment with thalidomide. Rev Med Interne 1998; 19: 196–198.

82. Li R, Lin T, Gu H et al. Successful thalidomide treatment of adult solitary perianal Langerhans cell histiocytosis. Eur J Dermatol 2010; 20: 391–392.

83. Mauro E, Fraulini C, Rigolin GM et al. A case of disseminated Langerhans’ cell histiocytosis treated with thalidomide. Eur J Haematol 2005; 74: 172–174.

84. McClain KL, Kozinetz CA. A phase II trial using thalidomide for Langerhans cell histiocytosis. Pediatr Blood Cancer 2007; 48: 44–49.

85. Meunier L, Marck Y, Ribeyre C et al. Adult cutaneous Langerhans cell histiocytosis: remission with thalidomide treatment. Br J Dermatol 1995; 132: 168.

86. Misery L, Larbre B, Lyonnet S et al. Remission of Langerhans cell histiocytosis with thalidomide treatment. Clin Exp Dermatol 1993; 18: 487.

87. Montero AJ, Díaz-Montero CM, Malpica A et al. Langerhans cell histiocytosis of the female genital tract: a literature review. Int J Gynecol Cancer 2003; 13: 381–388.

88. Moraes M, Russo G. Thalidomide and its dermatologic uses. Am J Med Sci 2001; 321: 321–326.

89. Sander CS, Kaatz M, Elsner P. Successful treatment of cutaneous langerhans cell histiocytosis with thalidomide. Dermatology 2004; 208: 149–152.

90. Moravvej H, Yousefi M, Barikbin B. An unusual case of adult disseminated cutaneous Langerhans cell histiocytosis. Dermatol Online J 2006; 12: 13.

91. Thomas L, Ducros B, Secchi T et al. Successful treatment of adult’s Langerhans cell histiocytosis with thalidomide. Report of two cases and literature review. Arch Dermatol 1993; 129: 1261–1264.

92. Wu JJ, Huang DB, Pang KR et al. Thalidomide: dermatological indications, mechanisms of action and side-effects. Br J Dermatol 2005; 153: 254–273.

93. Idbaih A, Donadieu J, Barthez MA et al. Retinoic acid therapy in “degenerative-like” neuro-langerhans cell histiocytosis: a prospective pilot study. Pediatr Blood Cancer 2004; 43: 55–58.

94. Kwinter J, DeKoven J. Generalized eruptive histiocytoma treated with isotretinoin. J Cutan Med Surg 2009; 13: 146–150.

95. Rayburg M, Towbin A, Yin H et al. Langerhans cell histiocytosis in a patient with stage 4 neuroblastoma receiving oral fenretinide. Pediatr Blood Cancer 2009; 53: 1111–1113.

96. Tsambaos D, Georgiou S, Kapranos N et al. Langerhans’ cell histiocytosis: complete remission after oral isotretinoin therapy. Acta Derm Venereol 1995; 75: 62–64.

97. Cardoso JC, Cravo M, Cardoso R et al. Langerhans cell histiocytosis in an adult: good response of cutaneous lesions to acitretin. Clin Exp Dermatol 2010; 35: 627–630.

98. Gebhardt C, Averbeck M, Paasch U et al. A case of cutaneous Rosai-Dorfman disease refractory to imatinib therapy. Arch Dermatol 2009; 145: 571–574.

99. Montella L, Insabato L, Palmieri G. Imatinib mesylate for cerebral Langerhans’-cell histiocytosis. N Engl J Med 2004; 351: 1034–1035.

100. Utikal J, Ugurel S, Kurzen H et al. Imatinib as a treatment option for systemic non-Langerhans cell histiocytoses. Arch Dermatol 2007; 143: 736–740.

101. Wagner C, Mohme H, Krömer-Olbrisch T et al. Langerhans cell histiocytosis: treatment failure with imatinib. Arch Dermatol 2009; 145: 949–950.

102. Jordan MB, McClain KL, Yan X et al. Anti-CD52 antibody, alemtuzumab, binds to Langerhans cells in Langerhans cell histiocytosis. Pediatr Blood Cancer 2005; 44: 251–254.

103. Munn SE, Olliver L, Broadbent V et al. Use of indomethacin in Langerhans cell histiocytosis. Med Pediatr Oncol 2001; 32: 247–249.

104. Park JW, Chung JW. Long-term treatment of Langerhans cell histiocytosis of the mandibular condyle with indomethacin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: e13–e21.

105. Lonsdale-Eccles AA, Haworth AE, McCrae FC et al. Successful treatment of multicentric reticulohistiocytosis with leflunomide. Br J Dermatol 2009; 161: 470–472.

106. Akkari V, Donadieu J, Piguet C et al. Hematopoietic stem cell transplantation in patients with severe Langerhans cell histiocytosis and hematological dysfunction: experience of the French Langerhans Cell Study Group. Bone Marrow Transplant 2003; 31: 1097–1103.

107. Berry J, Russell JA. Salvage of relapsed malignant histiocytosis by autologous bone marrow transplant. Bone Marrow Transplant 1989; 4: 123–124.

108. Caselli D, Aricò M. EBMT Paediatric Working Party. The role of BMT in childhood histiocytoses. Bone Marrow Transplant 2008; 41 (Suppl 2): S8–S13.

109. Conter V, Reciputo A, Arrigo C et al. Bone marrow transplantation for refractory Langerhans’ cell histiocytosis. Haematologica 1996; 81: 468–471.

110. Cooper N, Rao K, Goulden N et al. The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis. Bone Marrow Transplant 2008; 42 (Suppl 2): S47–S50.

111. Hale GA, Bowman LC, Woodard JP et al. Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen. Bone Marrow Transplant 2003; 31: 981–986.

112. Henter JI, Tondini C, Pritchard J. Histiocyte disorders. Crit Rev Oncol Hematol 2004; 50: 157–174.

113. Ichikawa K, Nomura S, Ishii K et al. Autologous stem cell transplantation for refractory Langerhans’ cell histiocytosis. Bone Marrow Transplant 2007; 40: 807–808.

114. Ingram W, Desai SR, Gibbs JS et al. Reduced-intensity conditioned allogeneic haematopoietic transplantation in an adult with Langerhans’ cell histiocytosis and thrombocytopenia with absent radii. Bone Marrow Transplant 2006; 37: 713–715.

115. Kesik V, Citak C, Kismet E et al. Hematopoietic stem cell transplantation in Langerhans cell histiocytosis: case report and review of the literature. Pediatr Transplant 2009; 13: 371–374.

116. Kinugawa N, Imashuku S, Hirota Y et al. Hematopoietic stem cell transplantation (HSCT) for Langerhans cell histiocytosis (LCH) in Japan. Bone Marrow Transplant 1999; 24: 935–938.

117. Meyer-Wentrup F, Foell J, Wawer A et al. Unrelated cord blood transplantation in an infant with severe multisystem Langerhans cell histiocytosis: clinical outcome, engraftment and culture of monocyte-derived dendritic cells. Bone Marrow Transplant 2004; 33: 875–876.

118. Nagarajan R, Neglia J, Ramsay N et al. Successful treatment of refractory Langerhans cell histiocytosis with unrelated cord blood transplantation. J Pediatr Hematol Oncol 2001; 23: 629–632.

119. 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: 215–225.

120. Stoll M, Freund M, Schmid H et al. Allogeneic bone marrow transplantation for Langerhans’ cell histiocytosis. Cancer 1990; 66: 284–288.

121. Suminoe A, Matsuzaki A, Hattori H et al. Unrelated cord blood transplantation for an infant with chemotherapy-resistant progressive Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2001; 23: 633–636.

122. Xicoy B, Ribera JM, Batlle M et al. Sustained remission in an adult patient with Langerhans cell histiocytosis following T-cell depleted allogenic cell transplantation. Med Clin (Barc) 2006; 127: 716.

123. Sulica R, Teirstein A, Padilla ML. Lung transplantation in interstitial lung disease. Curr Opin Pulm Med 2001; 7: 314–322.

124. Griffiths W, Davies S, Gibbs P et al. Liver transplantation in an adult with sclerosing cholangitis due Langerhans cell histiocytosis. J Hepatol 2006; 44: 829–831.

125. Goto H, Inaba M, Kobayashi K et al. Successful treatment of multicentric reticulohistiocytosis with alendronate: evidence for a direct effect of bisphosphonate on histiocytes. Arthritis Rheum 2003; 48: 3538–3541.

126. Hafeman S, London C, Elmslie R et al. Evaluation of liposomal clodronate for treatment of malignant histiocytosis in dogs. Cancer Immunol Immunother 2010; 59: 441–452.

127. Adamopoulos IE, Wordsworth PB, Edwards JR et al. Osteoclast differentiation and bone resorption in multicentric reticulohistiocytosis. Hum Pathol 2006; 37: 1176–1185.

128. Arzoo K, Sadeghi S, Pullarkar V. Pamidronate for bone pain from osteolytic lesions in Langerhans’ cell histiocytosis. N Engl J Med 2001; 345: 225–226.

129. Brown RE. Bisphosphonates as antialveolar macrophage therapy in pulmonary langerhans cell histiocytosis? Med Pediatr Oncol 2001; 36: 641–643.

130. Brown RE. More on pamidronate in Langerhans’-cell histiocytosis. N Engl J Med 2001; 345: 1503.

131. Codriansky KA, Rünger TM, Bhawan Jet al. Multicentric reticulohistiocytosis: a systemic osteoclastic disease? Arthritis Rheum 2008; 59: 444–448.

132. Egeler RM. More on pamidronate in Langerhans’ cell histiocytosis. N Engl J Med 2001; 345: 1502–1503.

133. Elomaa I, Blomqvist C, Porkka L et al. Experience of clodronate treatment of multifocal eosinophilic granuloma of bone. J Intern Med 1989; 225: 59–61.

134. Farran RP, Zaretski E, Egeler RM. Treatment of Langerhans cell histiocytosis with pamidronate. J Pediatr Hematol Oncol 2001; 23: 54–56.

135. Flores LG 2nd, Hoshi H, Nagamachi S et al. Thallium-201 uptake in eosinophilic granuloma of the frontal bone: comparison with technetium-99m-MDP imaging. J Nucl Med 1995; 36: 107–110.

136. Gibbons CL, Petra M, Smith R et al. Bisphosphonate treatment of benign multifocal and unifocal osteolytic tumours of bone. Sarcoma 2003; 7: 35–41.

137. Kamizono J, Okada Y, Shirahata A et al. Bisphosphonate induces remission of refractory osteolysis in langerhans cell histiocytosis. J Bone Miner Res 2002; 17: 1926–1928.

138. Mavragani CP, Batziou K, Aroni K et al. Alleviation of polyarticular syndrome in multicentric reticulohistiocytosis with intravenous zoledronate. Ann Rheum Dis 2005; 64: 1521–1522.

139. Montella L, Merola C, Merola G et al. Zoledronic acid in treatment of bone lesions by Langerhans cell histiocytosis. J Bone Miner Metab 2009; 27: 110–113.

140. Satoh M, Oyama N, Yamada H et al. Treatment trial of multicentric reticulohistiocytosis with a combination of prednisolone, methotrexate and alendronate. J Dermatol 2008; 35: 168–171.

141. Srikulmontree T, Massey HD, Roberts WN. Treatment of skeletal Erdheim-Chester disease with zoledronic acid: case report and proposed mechanisms of action. Rheumatol Int 2007; 27: 303–307.