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. 1994 Sep;23:S41–S46.

Treatment of Langerhans cell histiocytosis--evolution and current approaches.

S Ladisch 1, H Gadner 1
PMCID: PMC2149708  PMID: 8075005

Abstract

Optimal treatment of Langerhans cell histiocytosis remains problematic. The absence of controlled studies and the lack of standard diagnostic and evaluation criteria have impeded therapeutic progress even though knowledge of basic aspects of LCH have advanced. Historical analysis of outcome suggests little improvement until very recently, but marked differences in outcome according to extent of disease. Consequently, major and now successful efforts have been made to stratify LCH patients into different 'risk groups'. Recent findings suggest that combination chemotherapy for multisystem disease is beneficial and that VP-16 is a useful new agent for treating LCH, despite controversies regarding its side effects. The first randomised international treatment study, LCH-1, being conducted by the Histiocyte Society, should resolve some of these controversies. Other experimental therapies may be considered for children with severe, unresponsive LCH.

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Selected References

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  1. AVERY M. E., MCAFEE J. G., GUILD H. G. The course and prognosis of reticuloendotheliosis (eosinophilic granuloma, Schüller-Christian disease and Letterer-Siwe disease); a study of forty cases. Am J Med. 1957 Apr;22(4):636–652. doi: 10.1016/0002-9343(57)90115-8. [DOI] [PubMed] [Google Scholar]
  2. Aricò M. Cyclosporine therapy for refractory Langerhans cell histiocytosis. Blood. 1991 Dec 1;78(11):3107–3107. [PubMed] [Google Scholar]
  3. Bellmunt J., Albanell J., Salud A., Español T., Morales S., Solé-Calvo L. A. Interferon and disseminated Langerhans cell histiocytosis. Med Pediatr Oncol. 1992;20(4):336–337. doi: 10.1002/mpo.2950200413. [DOI] [PubMed] [Google Scholar]
  4. Berry D. H., Gresik M. V., Humphrey G. B., Starling K., Vietti T., Boyett J., Marcus R. Natural history of histiocytosis X: a Pediatric Oncology Group Study. Med Pediatr Oncol. 1986;14(1):1–5. doi: 10.1002/mpo.2950140102. [DOI] [PubMed] [Google Scholar]
  5. Broadbent V., Gadner H., Komp D. M., Ladisch S. Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Clinical Writing Group of the Histiocyte Society. Med Pediatr Oncol. 1989;17(6):492–495. doi: 10.1002/mpo.2950170527. [DOI] [PubMed] [Google Scholar]
  6. Broadbent V., Pritchard J., Davies E. G., Levinsky R. J., Heaf D., Atherton D. J., Pincott J. R., Tucker S. Spontaneous remission of multi-system histiocytosis X. Lancet. 1984 Feb 4;1(8371):253–254. doi: 10.1016/s0140-6736(84)90127-2. [DOI] [PubMed] [Google Scholar]
  7. Broadbent V., Pritchard J. Histiocytosis X--current controversies. Arch Dis Child. 1985 Jul;60(7):605–607. doi: 10.1136/adc.60.7.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Broadbent V., Pritchard J., Yeomans E. Etoposide (VP16) in the treatment of multisystem Langerhans cell histiocytosis (histiocytosis X). Med Pediatr Oncol. 1989;17(2):97–100. doi: 10.1002/mpo.2950170205. [DOI] [PubMed] [Google Scholar]
  9. Ceci A., de Terlizzi M., Colella R., Balducci D., Toma M. G., Zurlo M. G., Macchia P., Mancini A., Indolfi P., Locurto M. Etoposide in recurrent childhood Langerhans' cell histiocytosis: an Italian cooperative study. Cancer. 1988 Dec 15;62(12):2528–2531. doi: 10.1002/1097-0142(19881215)62:12<2528::aid-cncr2820621213>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  10. Ceci A., de Terlizzi M., Colella R., Loiacono G., Balducci D., Surico G., Castello M., Testi A. M., De Bernardi B., Indolfi P. Langerhans cell histiocytosis in childhood: results from the Italian Cooperative AIEOP-CNR-H.X '83 study. Med Pediatr Oncol. 1993;21(4):259–264. doi: 10.1002/mpo.2950210405. [DOI] [PubMed] [Google Scholar]
  11. Ceci A., de Terlizzi M., Toma M. G., Calculli G., Caputo R., Castello M., Indolfi P., Rosati D. Heterogeneity of immunological patterns in Langerhan's histiocytosis and response to crude calf thymic extract in 11 patients. Med Pediatr Oncol. 1988;16(2):111–115. doi: 10.1002/mpo.2950160209. [DOI] [PubMed] [Google Scholar]
  12. Daneshbod K., Kissane J. M. Idiopathic differentiated histiocytosis. Am J Clin Pathol. 1978 Sep;70(3):381–389. doi: 10.1093/ajcp/70.3.381. [DOI] [PubMed] [Google Scholar]
  13. Davies E. G., Levinsky R. J., Butler M., Broadbent V., Pritchard J., Chessells J. Thymic hormone therapy for histiocytosis X? N Engl J Med. 1983 Aug 25;309(8):493–494. [PubMed] [Google Scholar]
  14. Eckstein R., Huhn D., Schneider B., Heim M. U., Peltz F., Müller R., Edlmann M., Löhr G., Mempel W. Beeinflussung immunfunktioneller Parameter bei Histiozytose-X durch Thymostimulin. Arzneimittelforschung. 1985;35(1):155–162. [PubMed] [Google Scholar]
  15. Egeler R. M., de Kraker J., Voûte P. A. Cytosine-arabinoside, vincristine, and prednisolone in the treatment of children with disseminated Langerhans cell histiocytosis with organ dysfunction: experience at a single institution. Med Pediatr Oncol. 1993;21(4):265–270. doi: 10.1002/mpo.2950210406. [DOI] [PubMed] [Google Scholar]
  16. Feldges A. J. Childhood histiocytosis X: clinical aspects and therapeutic approaches. Haematol Blood Transfus. 1981;27:225–229. doi: 10.1007/978-3-642-81696-3_27. [DOI] [PubMed] [Google Scholar]
  17. Gadner H., Heitger A., Grois N., Gatterer-Menz I., Ladisch S. Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group. Med Pediatr Oncol. 1994;23(2):72–80. doi: 10.1002/mpo.2950230203. [DOI] [PubMed] [Google Scholar]
  18. Gramatovici R., D'Angio G. J. Radiation therapy in soft-tissue lesions in histiocytosis X (Langerhans' cell histiocytosis). Med Pediatr Oncol. 1988;16(4):259–262. doi: 10.1002/mpo.2950160407. [DOI] [PubMed] [Google Scholar]
  19. Greenberger J. S., Crocker A. C., Vawter G., Jaffe N., Cassady J. R. Results of treatment of 127 patients with systemic histiocytosis. Medicine (Baltimore) 1981 Sep;60(5):311–338. doi: 10.1097/00005792-198109000-00001. [DOI] [PubMed] [Google Scholar]
  20. Greinix H. T., Storb R., Sanders J. E., Petersen F. B. Marrow transplantation for treatment of multisystem progressive Langerhans cell histiocytosis. Bone Marrow Transplant. 1992 Jul;10(1):39–44. [PubMed] [Google Scholar]
  21. Halton J., Whitton A., Wiernikowski J., Barr R. D. Disseminated Langerhans cell histiocytosis in identical twins unresponsive to recombinant human alpha-interferon and total body irradiation. Am J Pediatr Hematol Oncol. 1992 Aug;14(3):269–272. doi: 10.1097/00043426-199208000-00016. [DOI] [PubMed] [Google Scholar]
  22. Hawkins M. M., Wilson L. M., Stovall M. A., Marsden H. B., Potok M. H., Kingston J. E., Chessells J. M. Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer. BMJ. 1992 Apr 11;304(6832):951–958. doi: 10.1136/bmj.304.6832.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jakobson A. M., Kreuger A., Hagberg H., Sundström C. Treatment of Langerhans cell histiocytosis with alpha-interferon. Lancet. 1987 Dec 26;2(8574):1520–1521. doi: 10.1016/s0140-6736(87)92649-3. [DOI] [PubMed] [Google Scholar]
  24. Komp D. M., El Mahdi A., Starling K. A., Easley J., Vietti T. J., Berry D. H., George S. L. Quality of survival in histiocytosis X: a Southwest Oncology Group study. Med Pediatr Oncol. 1980;8(1):35–40. doi: 10.1002/mpo.2950080106. [DOI] [PubMed] [Google Scholar]
  25. Komp D. M. Long-term sequelae of histiocytosis X. Am J Pediatr Hematol Oncol. 1981 Summer;3(2):163–168. [PubMed] [Google Scholar]
  26. Komp D. M., Vietti T. J., Berry D. H., Starling K. A., Haggard M. E., George S. L. Combination chemotherapy in histiocytosis X. Med Pediatr Oncol. 1977;3(3):267–273. doi: 10.1002/mpo.2950030308. [DOI] [PubMed] [Google Scholar]
  27. Ladisch S., Gadner H., Aricò M., Broadbent V., Grois N., Jacobson A., Komp D., Nicholson H. S. LCH-I: a randomized trial of etoposide vs. vinblastine in disseminated Langerhans cell histiocytosis. The Histiocyte Society. Med Pediatr Oncol. 1994;23(2):107–110. doi: 10.1002/mpo.2950230207. [DOI] [PubMed] [Google Scholar]
  28. Lahey E. Histiocytosis x--an analysis of prognostic factors. J Pediatr. 1975 Aug;87(2):184–189. doi: 10.1016/s0022-3476(75)80576-2. [DOI] [PubMed] [Google Scholar]
  29. Mahmoud H. H., Wang W. C., Murphy S. B. Cyclosporine therapy for advanced Langerhans cell histiocytosis. Blood. 1991 Feb 15;77(4):721–725. [PubMed] [Google Scholar]
  30. Matus-Ridley M., Raney R. B., Jr, Thawerani H., Meadows A. T. Histiocytosis X in children: patterns of disease and results of treatment. Med Pediatr Oncol. 1983;11(2):99–105. doi: 10.1002/mpo.2950110206. [DOI] [PubMed] [Google Scholar]
  31. McLelland J., Broadbent V., Yeomans E., Malone M., Pritchard J. Langerhans cell histiocytosis: the case for conservative treatment. Arch Dis Child. 1990 Mar;65(3):301–303. doi: 10.1136/adc.65.3.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Neumann C., Kolde G., Bonsmann G. Histiocytosis X in an elderly patient. Ultrastructure and immunocytochemistry after PUVA photochemotherapy. Br J Dermatol. 1988 Sep;119(3):385–391. doi: 10.1111/j.1365-2133.1988.tb03233.x. [DOI] [PubMed] [Google Scholar]
  33. Nezelof C., Frileux-Herbet F., Cronier-Sachot J. Disseminated histiocytosis X: analysis of prognostic factors based on a retrospective study of 50 cases. Cancer. 1979 Nov;44(5):1824–1838. doi: 10.1002/1097-0142(197911)44:5<1824::aid-cncr2820440542>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  34. OBERMAN H. A. A clinicopathologic study of 40 cases and review of the literature on eosinophilic granuloma of bone. Hand-Schuller-Christian disease and Letterer-Siwe disease. Pediatrics. 1961 Aug;28:307–327. [PubMed] [Google Scholar]
  35. Osband M. E., Lipton J. M., Lavin P., Levey R., Vawter G., Greenberger J. S., McCaffrey R. P., Parkman R. Histiocytosis-X. N Engl J Med. 1981 Jan 15;304(3):146–153. doi: 10.1056/NEJM198101153040304. [DOI] [PubMed] [Google Scholar]
  36. Raney R. B., Jr, D'Angio G. J. Langerhans' cell histiocytosis (histiocytosis X): experience at the Children's Hospital of Philadelphia, 1970-1984. Med Pediatr Oncol. 1989;17(1):20–28. doi: 10.1002/mpo.2950170106. [DOI] [PubMed] [Google Scholar]
  37. Ringdén O., Ahström L., Lönnqvist B., Båryd I., Svedmyr E., Gahrton G. Allogeneic bone marrow transplantation in a patient with chemotherapy-resistant progressive histiocytosis X. N Engl J Med. 1987 Mar 19;316(12):733–735. doi: 10.1056/NEJM198703193161207. [DOI] [PubMed] [Google Scholar]
  38. Selch M. T., Parker R. G. Radiation therapy in the management of Langerhans cell histiocytosis. Med Pediatr Oncol. 1990;18(2):97–102. doi: 10.1002/mpo.2950180203. [DOI] [PubMed] [Google Scholar]
  39. Sheehan M. P., Atherton D. J., Broadbent V., Pritchard J. Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis. J Pediatr. 1991 Aug;119(2):317–321. doi: 10.1016/s0022-3476(05)80752-8. [DOI] [PubMed] [Google Scholar]
  40. Stoll M., Freund M., Schmid H., Deicher H., Riehm H., Poliwoda H., Link H. Allogeneic bone marrow transplantation for Langerhans' cell histiocytosis. Cancer. 1990 Jul 15;66(2):284–288. doi: 10.1002/1097-0142(19900715)66:2<284::aid-cncr2820660215>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  41. Toogood I. R., Ellis W. M., Ekert H. Prognostic criteria, treatment and survival in disseminated histiocytosis X. Aust Paediatr J. 1979 Jun;15(2):91–95. doi: 10.1111/j.1440-1754.1979.tb01196.x. [DOI] [PubMed] [Google Scholar]
  42. Viana M. B., Oliveira B. M., Silva C. M., Rios Leite V. H. Etoposide in the treatment of six children with Langerhans cell histiocytosis (histiocytosis X) Med Pediatr Oncol. 1991;19(4):289–294. doi: 10.1002/mpo.2950190414. [DOI] [PubMed] [Google Scholar]

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