Langerhans Cell Histiocytosis in Adults: Treatment Opportunities of Today

VD Latyshev, EA Lukina

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Vitalii Dmitrievich Latyshev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: LatyshevVD@gmail.com

For citation: Latyshev VD, Lukina EA. Langerhans Cell Histiocytosis in Adults: Treatment Opportunities of Today. Clinical oncohematology. 2021;14(4):444–54. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-444-454


ABSTRACT

Langerhans cell histiocytosis (LCH) is an extremely rare disease associated with tissue infiltration by pathological cells which are phenotypically similar to normal Langerhans cells. Standard therapy of LCH in adults has not been developed so far, due to the lack of sufficient evidence base for different treatment methods. In clinical practice, cytostatic treatment is applied along with new approaches using signaling pathway inhibitors involved in LCH pathogenesis. This literature review covers currently existing methods of LCH therapy in adults and their feasibility in clinical practice.

Keywords: Langerhans cell histiocytosis, treatment of histiocytosis, BRAFV600E mutation, MAPK.

Received: July 20, 2021

Accepted: September 23, 2021

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Статистика Plumx английский

REFERENCES

  1. Лукина Е.А., Козловская А.С., Капланская И.Б., Мокеева Р.А. Гистиоцитоз X — Гистиоцитоз из клеток Лангерганса. Гематология и трансфузиология. 1990;35(9):10–5.
    [Lukina EA, Kozlovskaya AS, Kaplanskaya IB, Mokeeva RA. Histiocytosis X — Langerhans cell histiocytosis. Gematologiya i transfuziologiya. 1990;35(9):10–5. (In Russ)]
  2. Yu RC, Chu AC, Chu C, et al. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet. 1994;343(8900):767–8. doi: 10.1016/S0140-6736(94)91842-2.
  3. Willman CL, Busque L, Griffith BB, et al. Langerhans’-Cell Histiocytosis (Histiocytosis X) — A Clonal Proliferative Disease. N Engl J Med. 1994;331(3):154–60. doi: 10.1056/NEJM199407213310303.
  4. Badalian-Very G, Vergilio J-A, Degar BA, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010;116(11):1919–23. doi: 10.1182/blood-2010-04-279083.
  5. Braier J. Is Langerhans cell histiocytosis a neoplasia? Pediatr Blood Cancer. 2017;64(3):e26267. doi: 10.1002/pbc.26267.
  6. Egeler RM, Katewa S, Leenen PJM, et al. Langerhans cell histiocytosis is a neoplasm and consequently its recurrence is a relapse: In memory of Bob Arceci. Pediatr Blood Cancer. 2016;63(10):1704–12. doi: 10.1002/pbc.26104.
  7. Collin M, Bigley V, McClain KL, et al. Cell(s) of Origin of Langerhans Cell Histiocytosis. Hematol Oncol Clin North Am. 2015;29(5):825–38. doi: 10.1016/j.hoc.2015.06.003.
  8. Allen CE, Beverley PCL, Collin M, et al. The coming of age of Langerhans cell histiocytosis. Nat Immunol. 2020;21(1):1–7. doi: 10.1038/s41590-019-0558-z.
  9. Allen CE, Merad M, McClain KL. Langerhans-Cell Histiocytosis. N Engl J Med. 2018;379(9):856–68. doi: 10.1056/NEJMra1607548.
  10. Girschikofsky M, Arico M, Castillo D, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis. 2013;8(1):72. doi: 10.1186/1750-1172-8-72.
  11. Key SJ, O’Brien CJ, Silvester KC, et al. Eosinophilic granuloma: resolution of maxillofacial bony lesions following minimal intervention. Report of three cases and a review of the literature. J Cranio-Maxillofac Surg. 2004;32(3):170–5. doi: 10.1016/j.jcms.2004.01.004.
  12. Namai T, Yusa H, Yoshida H. Spontaneous remission of a solitary eosinophilic granuloma of the mandible after biopsy: A case report. J Oral Maxillofac Surg. 2001;59(12):1485–7. doi: 10.1053/joms.2001.28290.
  13. 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 Endodontol. 2010;109(2):e53–8. doi: 10.1016/j.tripleo.2009.10.015.
  14. Watzke IM, Millesi W, Kermer C, et al. Multifocal eosinophilic granuloma of the jaw: Long-term follow-up of a novel intraosseous corticoid treatment for recalcitrant lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol. 2000;90(3):317–22. doi: 10.1067/moe.2000.107535.
  15. Almuzayyen A, Elhassan W, Alabbadi M. Intralesional triamcinolone for treating mandibular Langerhans cell histiocytosis: A case report and literature review. Saudi J Med Med Sci. 2019;7(1):47. doi: 10.4103/sjmms.sjmms_84_17.
  16. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121(25):5006–14. doi: 10.1182/blood-2012-09-455774.
  17. Minkov M. Multisystem Langerhans Cell Histiocytosis in Children. Pediatr Drugs. 2011;13(2):75–86. doi: 10.2165/11538540-000000000-00000.
  18. Cantu MA, Lupo PJ, Bilgi M, et al. Optimal Therapy for Adults with Langerhans Cell Histiocytosis Bone Lesions. PLoS One. 2012;7(8):e43257. doi: 10.1371/journal.pone.0043257.
  19. Tazi A, Lorillon G, Haroche J, et al. Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study. Orphanet J Rare Dis. 2017;12(1):95. doi: 10.1186/s13023-017-0651-z.
  20. 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(12):1415–23. doi: 10.1182/blood-2015-03-635151.
  21. Saven A, Figueroa ML, Piro LD, et al. 2-Chlorodeoxyadenosine to Treat Refractory Histiocytosis X. N Engl J Med. 1993;329(10):734–5. doi: 10.1056/NEJM199309023291013.
  22. Saven A, Burian C. Cladribine Activity in Adult Langerhans-Cell Histiocytosis. Blood. 1999;93(12):4125–30. doi: 10.1182/blood.V93.12.4125.
  23. Adam Z, Szturz P, Vanicek J, et al. Cladribine (2-chlorodeoxyadenosine) in frontline chemotherapy for adult Langerhans cell histiocytosis: A single-center study of seven cases. Acta Oncol (Madr). 2013;52(5):994–1001. doi: 10.3109/0284186X.2012.716164.
  24. Allen CE, Ladisch S, McClain KL. How I treat Langerhans cell histiocytosis. Blood. 2015;126(1):26–35. doi: 10.1182/blood-2014-12-569301.
  25. Friedman B, Cronstein B. Methotrexate mechanism in treatment of rheumatoid arthritis. Jt Bone Spine. 2019;86(3):301–7. doi: 10.1016/j.jbspin.2018.07.004.
  26. Steen AE, Steen KH, Bauer R, et al. Successful treatment of cutaneous Langerhans cell histiocytosis with low-dose methotrexate. Br J Dermatol. 2001;145(1):137–40. doi: 10.1046/j.1365-2133.2001.04298.x.
  27. Cao X, Li J, Zhao A, et al. Methotrexate and Cytarabine for Adult Patients with Newly Diagnosed Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study. Blood. 2019;134(Suppl_1):294. doi: 10.1182/blood-2019-122220.
  28. Derenzini E, Stefoni V, Pellegrini C, et al. High efficacy of the MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis, a 20 year experience. BMC Cancer. 2015;15(1):879. doi: 10.1186/s12885-015-1903-8.
  29. Tanimura S, Takeda K. ERK signalling as a regulator of cell motility. J Biochem. 2017;162(3):145–54. doi: 10.1093/jb/mvx048.
  30. Ducreux M, Chamseddine A, Laurent-Puig P, et al. Molecular targeted therapy of BRAF-mutant colorectal cancer. Ther Adv Med Oncol. 2019;11:175883591985649. doi: 10.1177/1758835919856494.
  31. Falini B, Martelli MP, Tiacci E. BRAF V600E mutation in hairy cell leukemia: from bench to bedside. Blood. 2016;128(15):1918–27. doi: 10.1182/blood-2016-07-418434.
  32. Emile J-F, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127(22):2672–81. doi: 10.1182/blood-2016-01-690636.
  33. Крылов А.С., Долгушин М.Б., Рыжков А.Д. и др. Болезнь Эрдгейма–Честера. Обзор литературы и клинический случай. Онкогематология. 2020;15(2):61–75. doi: 10.17650/1818-8346-2020-15-2-61-75.
    [Krylov AS, Dolgushin MB, Ryzhkov AD, et al. Erdheim-Chester disease. Literature review and clinical case. Oncohematology. 2020;15(2):61–75. doi: 10.17650/1818-8346-2020-15-2-61-75. (In Russ)]
  34. Chakraborty R, Burke TM, Hampton OA, et al. Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis. Blood. 2016;128(21):2533–7. doi: 10.1182/blood-2016-08-733790.
  35. Diamond EL, Subbiah V, Lockhart AC, et al. Vemurafenib for BRAF V600–Mutant Erdheim-Chester Disease and Langerhans Cell Histiocytosis. JAMA Oncol. 2018;4(3):384. doi: 10.1001/jamaoncol.2017.5029.
  36. Haroche J, Cohen-Aubart F, Emile J-F, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013;121(9):1495–500. doi: 10.1182/blood-2012-07-446286.
  37. Ruan G, Goyal G, Abeykoon JP, et al. Low-Dose BRAF-Inhibitors in the Treatment of Histiocytic Disorders with the BRAF-V600E Mutation. Blood. 2019;134(Suppl_1):5895. doi: 10.1182/blood-2019-124891.
  38. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations. N Engl J Med. 2012;367(18):1694–703. doi: 10.1056/NEJMoa1210093.
  39. Papapanagiotou M, Griewank KG, Hillen U, et al. Trametinib-Induced Remission of an MEK1-Mutated Langerhans Cell Histiocytosis. JCO Precis Oncol. 2017;1:1–5. doi: 10.1200/PO.16.00070.
  40. Lorillon G, Jouenne F, Baroudjian B, et al. Response to Trametinib of a Pulmonary Langerhans Cell Histiocytosis Harboring a MAP2K1 Deletion. Am J Respir Crit Care Med. 2018;198(5):675–8. doi: 10.1164/rccm.201802-0275LE.
  41. Sullivan RJ, Infante JR, Janku F, et al. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discov. 2018;8(2):184–95. doi: 10.1158/2159-8290.CD-17-1119.
  42. Smalley I, Smalley KSM. ERK Inhibition: A New Front in the War against MAPK Pathway–Driven Cancers? Cancer Discov. 2018;8(2):140–2. doi: 10.1158/2159-8290.CD-17-1355.
  43. Sosman MC. Xanthomatosis. J Am Med Assoc. 1932;98(2):110. doi: 10.1001/jama.1932.02730280018005.
  44. Kriz J, Eich H, Bruns F, et al. Radiotherapy in Langerhans cell histiocytosis – a rare indication in a rare disease. Radiat Oncol. 2013;8(1):233. doi: 10.1186/1748-717X-8-233.
  45. Olschewski T, Seegenschmiedt MH. Radiotherapy of Langerhans’ Cell Histiocytosis. Strahlenther Onkol. 2006;182(11):629–34. doi: 10.1007/s00066-006-1630-9.
  46. Greenberger JS, Crocker AC, Vawter G, et al. Results of Treatment of 127 Patients with Systemic Histiocytosis (Letterer-Siwe Syndrome, Schuller-Christian Syndrome and Multifocal Eosinophilic Granuloma). Medicine (Baltimore). 1981;60(5):311–38. doi: 10.1097/00005792-198109000-00001.
  47. Furudate S, Fujimura T, Kambayashi Y, et al. Successful Treatment of Adult Onset Langerhans Cell Histiocytosis with Bi-weekly Administration of Pegylated Interferon-α. Acta Derm Venereol. 2014;94(5):611–2. doi: 10.2340/00015555-1807.
  48. El-Safadi S, Dreyer T, Oehmke F, et al. Management of adult primary vulvar Langerhans cell histiocytosis: review of the literature and a case history. Eur J Obstet Gynecol Reprod Biol. 2012;163(2):123–8. doi: 10.1016/j.ejogrb.2012.03.010.
  49. Ibrahim IF, Naina HVK. Treatment of recurrent Langerhans cell histiocytosis of the vulva with lenalidomide. J Clin Oncol. 2013;31(15_suppl):e16555. doi: 10.1200/jco.2013.31.15_suppl.e16555.
  50. Лукина Е.А., Кузнецов В.П., Беляев Д.Л. и др. Лечение гистиоцитоза Х (гистиоцитоз из клеток Лангерганса) препаратами α-интерферона. Терапевтический архив. 1993;11(65):67–70.
    [Lukina EA, Kuznetsov VP, Belyaev DL, et al. The treatment of histiocytosis X (Langerhans-cell histiocytosis) with alpha-interferon preparations. Terapevticheskii arkhiv. 1993;11(65):67–70. (In Russ)]
  51. Szturz P, Adam Z, Rehak Z, et al. Lenalidomide proved effective in multisystem Langerhans cell histiocytosis. Acta Oncol (Madr). 2012;51(3):412–5. doi: 10.3109/0284186X.2011.631581.
  52. Zinn DJ, Grimes AB, Lin H, et al. Hydroxyurea: a new old therapy for Langerhans cell histiocytosis. Blood. 2016;128(20):2462–5. doi: 10.1182/blood-2016-06-721993.
  53. Fleisch H. Bisphosphonates: Mechanisms of Action. Endocr Rev. 1998;19(1):80–100. doi: 10.1210/edrv.19.1.0325.
  54. Sivendran S, Harvey H, Lipton A, et al. Treatment of Langerhans cell histiocytosis bone lesions with zoledronic acid: a case series. Int J Hematol. 2011;93(6):782–6. doi: 10.1007/s12185-011-0839-2.
  55. Lebret T, Casas A, Cavo M, et al. The use of bisphosphonates in the management of bone involvement from solid tumours and haematological malignancies – a European survey. Eur J Cancer Care (Engl). 2017;26(4):e12490. doi: 10.1111/ecc.12490.
  56. 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(1):110–3. doi: 10.1007/s00774-008-0001-2.
  57. Elomaa I, Blomqvist C, Porkka L, et al. Experiences of clodronate treatment of multifocal eosinophilic granuloma of bone. J Intern Med. 1989;225(1):59–61. doi: 10.1111/j.1365-2796.1989.tb00038.x.
  58. Arzoo K, Sadeghi S, Pullarkat V. Pamidronate for Bone Pain from Osteolytic Lesions in Langerhans’-Cell Histiocytosis. N Engl J Med. 2001;345(3):225. doi: 10.1056/NEJM200107193450318.
  59. Weitzman R, Sauter N, Eriksen EF, et al. Critical review: Updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients—May 2006. Crit Rev Oncol Hematol. 2007;62(2):148–52. doi: 10.1016/j.critrevonc.2006.12.005.
  60. Makras P, Tsoli M, Anastasilakis AD, et al. Denosumab for the treatment of adult multisystem Langerhans cell histiocytosis. Metabolism. 2017;69:107–11. doi: 10.1016/j.metabol.2017.01.004.
  61. Pan Y, Xi R, Wang C, et al. Autologous hematopoietic stem cell transplantation for efficient treatment of multisystem, high-risk, BRAF V600E-negative Langerhans cell histiocytosis. J Int Med Res. 2019;47(9):4522–9. doi: 10.1177/0300060519864807.
  62. Braier J, Rosso D, Pollono D, et al. Symptomatic Bone Langerhans Cell Histiocytosis Treated at Diagnosis or After Reactivation With Indomethacin Alone. J Pediatr Hematol Oncol. 2014;36(5):e280–е284. doi: 10.1097/MPH.0000000000000165001.
  63. gov [Internet]. LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis. Identifier NCT02205762. Available from: https://clinicaltrials.gov/ct2/show/NCT02205762 (accessed 21.07.2021).
  64. Kurtulmus N, Mert M, Tanakol R, et al. The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation. Endocrine. 2015;48(3):949–56. doi: 10.1007/s12020-014-0408-6.
  65. Kaltsas GA, Powles TB, Evanson J, et al. Hypothalamo-Pituitary Abnormalities in Adult Patients with Langerhans Cell Histiocytosis: Clinical, Endocrinological, and Radiological Features and Response to Treatment. J Clin Endocrinol Metab. 2000;85(4):1370–6. doi: 10.1210/jcem.85.4.6501.
  66. Abla O, Janka G, eds. Histiocytic Disorders. Cham: Springer International Publishing; 2018. doi: 10.1007/978-3-319-59632-7.
  67. Hutter C, Minkov M. Insights into the pathogenesis of Langerhans cell histiocytosis: the development of targeted therapies. ImmunoTarg Ther. 2016;5:81–91. doi: 10.2147/itt.s91058.