Skip to main content
SpringerLink
Log in

Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors

  • Review Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Histiocytic disorders are rare diseases defined by the clonal accumulation of a macrophage or dendritic cell origin. These disorders include Langerhans cell histiocytosis, Erdheim–Chester disease, juvenile xanthogranuloma, malignant histiocytoses, and Rosai–Dorfman–Destombes disease. These histiocytic disorders are a diverse group of disorders with different presentations, management, and prognosis. This review focuses on these histiocytic disorders and the role of pathological ERK signaling due to somatic mutations in the mitogen­-activated protein kinase (MAPK) pathway. Over the last decade, there has been growing awareness of the MAPK pathway being a key driver in many histiocytic disorders, which has led to successful treatment with targeted therapies, in particular, BRAF inhibitors and MEK inhibitors.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Emile JF, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127(22):2672–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010;116(11):1919–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Samatar AA, Poulikakos PI. Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov. 2014;13(12):928–42.

    CAS  PubMed  Google Scholar 

  4. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.

    CAS  PubMed  Google Scholar 

  5. Braicu C, Buse M, Busuioc C, Drula R, Gulei D, Raduly L, et al. A comprehensive review on MAPK: a promising therapeutic target in cancer. Cancers (Basel). 2019;11(10):1618.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. McClain KL, Bigenwald C, Collin M, Haroche J, Marsh RA, Merad M, et al. Histiocytic disorders. Nat Rev Dis Primers. 2021;7(1):73.

    PubMed  PubMed Central  Google Scholar 

  7. Allen CE, Li L, Peters TL, Leung HC, Yu A, Man TK, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol. 2010;184(8):4557–67.

    CAS  PubMed  Google Scholar 

  8. Stålemark H, Laurencikas E, Karis J, Gavhed D, Fadeel B, Henter JI. Incidence of Langerhans cell histiocytosis in children: a population-based study. Pediatr Blood Cancer. 2008;51(1):76–81.

    PubMed  Google Scholar 

  9. Goyal G, Shah MV, Hook CC, Wolanskyj AP, Call TG, Rech KL, et al. Adult disseminated Langerhans cell histiocytosis: incidence, racial disparities and long-term outcomes. Br J Haematol. 2018;182(4):579–81.

    PubMed  Google Scholar 

  10. Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121(25):5006–14.

    CAS  PubMed  Google Scholar 

  11. Merad M, Ginhoux F, Collin M. Origin, homeostasis and function of Langerhans cells and other Langerin-expressing dendritic cells. Nat Rev Immunol. 2008;8(12):935–47.

    CAS  PubMed  Google Scholar 

  12. Yeh EA, Greenberg J, Abla O, et al. Evaluation and treatment of Langerhans cell histiocytosis patients with central nervous system abnormalities: current views and new vistas. Pediatr Blood Cancer. 2018;65:e26784. https://doi.org/10.1002/pbc.26784.

    Article  Google Scholar 

  13. Donadieu J, Rolon MA, Thomas C, Brugieres L, Plantaz D, Emile JF, et al. Endocrine involvement in pediatric-onset Langerhans’ cell histiocytosis: a population-based study. J Pediatr. 2004;144(3):344–50.

    PubMed  Google Scholar 

  14. Milne P, Bigley V, Bacon CM, Néel A, McGovern N, Bomken S, et al. Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults. Blood. 2017;130(2):167–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Durham BH, Roos-Weil D, Baillou C, Cohen-Aubart F, Yoshimi A, Miyara M, et al. Functional evidence for derivation of systemic histiocytic neoplasms from hematopoietic stem/progenitor cells. Blood. 2017;130(2):176–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Brown NA, Furtado LV, Betz BL, Kiel MJ, Weigelin HC, Lim MS, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood. 2014;124(10):1655–8.

    CAS  PubMed  Google Scholar 

  17. Chakraborty R, Hampton OA, Shen X, Simko SJ, Shih A, Abhyankar H, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124(19):3007–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Durham BH, Lopez Rodrigo E, Picarsic J, Abramson D, Rotemberg V, De Munck S, et al. Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms. Nat Med. 2019;25(12):1839–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Mourah S, How-Kit A, Meignin V, Gossot D, Lorillon G, Bugnet E, et al. Recurrent NRAS mutations in pulmonary Langerhans cell histiocytosis. Eur Respir J. 2016;47(6):1785–96.

    CAS  PubMed  Google Scholar 

  20. Nelson DS, van Halteren A, Quispel WT, van den Bos C, Bovée JV, Patel B, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer. 2015;54(6):361–8.

    CAS  PubMed  Google Scholar 

  21. Nelson DS, Quispel W, Badalian-Very G, van Halteren AG, van den Bos C, Bovée JV, et al. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood. 2014;123(20):3152–5.

    CAS  PubMed  Google Scholar 

  22. Lee LH, Gasilina A, Roychoudhury J, Clark J, McCormack FX, Pressey J, et al. Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes. JCI Insight. 2017;2(3): e89473.

    PubMed  PubMed Central  Google Scholar 

  23. Chakraborty R, Burke TM, Hampton OA, Zinn DJ, Lim KP, Abhyankar H, et al. Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis. Blood. 2016;128(21):2533–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Simko SJ, Garmezy B, Abhyankar H, Lupo PJ, Chakraborty R, Lim KP, et al. Differentiating skin-limited and multisystem Langerhans cell histiocytosis. J Pediatr. 2014;165(5):990–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Yasko AW, Fanning CV, Ayala AG, Carrasco CH, Murray JA. Percutaneous techniques for the diagnosis and treatment of localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone). J Bone Joint Surg Am. 1998;80(2):219–28.

    CAS  PubMed  Google Scholar 

  26. Farran RP, Zaretski E, Egeler RM. Treatment of Langerhans cell histiocytosis with pamidronate. J Pediatr Hematol Oncol. 2001;23(1):54–6.

    CAS  PubMed  Google Scholar 

  27. Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, et al. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015;126(12):1415–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Veys PA, Nanduri V, Baker KS, He W, Bandini G, Biondi A, et al. Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning. Br J Haematol. 2015;169(5):711–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Héritier S, Jehanne M, Leverger G, Emile JF, Alvarez JC, Haroche J, et al. Vemurafenib use in an infant for high-risk Langerhans cell histiocytosis. JAMA Oncol. 2015;1(6):836–8.

    PubMed  Google Scholar 

  30. Donadieu J, Larabi IA, Tardieu M, Visser J, Hutter C, Sieni E, et al. Vemurafenib for refractory multisystem Langerhans cell histiocytosis in children: an international observational study. J Clin Oncol. 2019;37(31):2857–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Eckstein OS, Visser J, Rodriguez-Galindo C, Allen CE, Group N-LS. Clinical responses and persistent BRAF V600E + blood cells in children with LCH treated with MAPK pathway inhibition. Blood. 2019;133(15):1691–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Kolenová A, Schwentner R, Jug G, Simonitsch-Klupp I, Kornauth C, Plank L, et al. Targeted inhibition of the MAPK pathway: emerging salvage option for progressive life-threatening multisystem LCH. Blood Adv. 2017;1(6):352–6.

    PubMed  PubMed Central  Google Scholar 

  33. McClain KL, Picarsic J, Chakraborty R, Zinn D, Lin H, Abhyankar H, et al. CNS Langerhans cell histiocytosis: common hematopoietic origin for LCH-associated neurodegeneration and mass lesions. Cancer. 2018;124(12):2607–20.

    CAS  PubMed  Google Scholar 

  34. Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte 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.

    CAS  PubMed  Google Scholar 

  35. Goyal G, Heaney ML, Collin M, Cohen-Aubart F, Vaglio A, Durham BH, et al. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. Blood. 2020;135(22):1929–45.

    CAS  PubMed  Google Scholar 

  36. Hervier B, Haroche J, Arnaud L, Charlotte F, Donadieu J, Néel A, et al. Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood. 2014;124(7):1119–26.

    CAS  PubMed  Google Scholar 

  37. Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, et al. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol. 2015;33(5):411–8.

    CAS  PubMed  Google Scholar 

  38. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373(8):726–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Diamond EL, Subbiah V, Lockhart AC, Blay JY, Puzanov I, Chau I, et al. Vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis: analysis of data from the histology-independent, phase 2, open-label VE-BASKET study. JAMA Oncol. 2018;4(3):384–8.

    PubMed  Google Scholar 

  40. Cohen Aubart F, Emile JF, Carrat F, Charlotte F, Benameur N, Donadieu J, et al. Targeted therapies in 54 patients with Erdheim-Chester disease, including follow-up after interruption (the LOVE study). Blood. 2017;130(11):1377–80.

    PubMed  Google Scholar 

  41. Haroche J, Abla O. Uncommon histiocytic disorders: Rosai-Dorfman, juvenile xanthogranuloma, and Erdheim-Chester disease. Hematology Am Soc Hematol Educ Program. 2015;2015:571–8.

    PubMed  Google Scholar 

  42. Simko SJ, Tran HD, Jones J, Bilgi M, Beaupin LK, Coulter D, et al. Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease. Pediatr Blood Cancer. 2014;61(3):479–87.

    CAS  PubMed  Google Scholar 

  43. Stover DG, Alapati S, Regueira O, Turner C, Whitlock JA. Treatment of juvenile xanthogranuloma. Pediatr Blood Cancer. 2008;51(1):130–3.

    PubMed  Google Scholar 

  44. Blouin P, Yvert M, Arbion F, Pagnier A, Emile JF, Eitenschenck L, et al. Juvenile xanthogranuloma with hematological dysfunction treated with 2CDA-AraC. Pediatr Blood Cancer. 2010;55(4):757–60.

    PubMed  Google Scholar 

  45. Techavichit P, Sosothikul D, Chaichana T, Teerapakpinyo C, Thorner PS, Shuangshoti S. BRAF V600E mutation in pediatric intracranial and cranial juvenile xanthogranuloma. Hum Pathol. 2017;69:118–22.

    CAS  PubMed  Google Scholar 

  46. Picarsic J, Pysher T, Zhou H, Fluchel M, Pettit T, Whitehead M, et al. BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease. Acta Neuropathol Commun. 2019;7(1):168.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Diamond EL, Durham BH, Haroche J, Yao Z, Ma J, Parikh SA, et al. Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov. 2016;6(2):154–65.

    CAS  PubMed  Google Scholar 

  48. Eissa SS, Clay MR, Santiago T, Wu G, Wang L, Shulkin BL, et al. Dasatinib induces a dramatic response in a child with refractory juvenile xanthogranuloma with a novel MRC1-PDGFRB fusion. Blood Adv. 2020;4(13):2991–5.

    PubMed  PubMed Central  Google Scholar 

  49. Abla O, Halliday W, Laughlin S, Weitzman S. Central nervous system juvenile xanthogranuloma after langerhans cell histiocytosis. Pediatr Blood Cancer. 2013;60(2):342–3.

    PubMed  Google Scholar 

  50. Nofal A, Assaf M, Tawfik A, Elsayed N, Nofal E, Elnakib N, et al. Progressive nodular histiocytosis: a case report and literature review. Int J Dermatol. 2011;50(12):1546–51.

    PubMed  Google Scholar 

  51. Berce PC, Cardwell L, Essenmacher AN, Michaelis LC, Wanat KA. Progressive nodular histiocytosis with dramatic response to cobimetinib. JAAD Case Rep. 2022;22:110–3.

    PubMed  PubMed Central  Google Scholar 

  52. Buján MM, Sánchez La Rosa C, Galluzzo Mutti ML, Braier J, Diamond EL. Progressive nodular histiocytosis in a 9-year-old boy treated with cobimetinib. Pediatr Dermatol. 2022;39(1):115–8.

    PubMed  Google Scholar 

  53. Abla O, Jacobsen E, Picarsic J, Krenova Z, Jaffe R, Emile JF, et al. Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease. Blood. 2018;131(26):2877–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Richardson TE, Wachsmann M, Oliver D, Abedin Z, Ye D, Burns DK, et al. BRAF mutation leading to central nervous system rosai-dorfman disease. Ann Neurol. 2018;84(1):147–52.

    CAS  PubMed  Google Scholar 

  55. Mastropolo R, Close A, Allen SW, McClain KL, Maurer S, Picarsic J. BRAF-V600E-mutated Rosai-Dorfman-Destombes disease and Langerhans cell histiocytosis with response to BRAF inhibitor. Blood Adv. 2019;3(12):1848–53.

    PubMed  PubMed Central  Google Scholar 

  56. Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, et al. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019;567(7749):521–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Jacobsen E, Shanmugam V, Jagannathan J. Rosai-Dorfman disease with activating KRAS mutation: response to cobimetinib. N Engl J Med. 2017;377(24):2398–9.

    PubMed  Google Scholar 

  58. Moyon Q, Boussouar S, Maksud P, Emile JF, Charlotte F, Aladjidi N, et al. Lung involvement in Destombes-Rosai-Dorfman disease: clinical and radiological features and response to the MEK inhibitor cobimetinib. Chest. 2020;157(2):323–33.

    CAS  PubMed  Google Scholar 

  59. Jacobsen E, Abla O, Visser J. Malignant histiocytoses. In: Abla O, Janka G, editors. Histiocytic disorders. Cham: Springer; 2018. p. 361–81.

    Google Scholar 

  60. Go H, Jeon YK, Huh J, Choi SJ, Choi YD, Cha HJ, et al. Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology. 2014;65(2):261–72.

    PubMed  Google Scholar 

  61. Hu B, Patel JL, Tao R, Cannon RB, Monroe M, Goyal G. Near complete response to trametinib treatment in histiocytic sarcoma harboring a somatic KRAS mutation. J Natl Compr Canc Netw. 2022;20(6):618–21.

    PubMed  Google Scholar 

  62. Gounder MM, Solit DB, Tap WD. Trametinib in histiocytic sarcoma with an activating MAP2K1 (MEK1) mutation. N Engl J Med. 2018;378(20):1945–7.

    PubMed  PubMed Central  Google Scholar 

  63. Gounder M, Desai V, Kuk D, Agaram N, Arcila M, Durham B, et al. Impact of surgery, radiation and systemic therapy on the outcomes of patients with dendritic cell and histiocytic sarcomas. Eur J Cancer. 2015;51(16):2413–22.

    PubMed  PubMed Central  Google Scholar 

  64. Kommalapati A, Tella SH, Durkin M, Go RS, Goyal G. Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes. Blood. 2018;131(2):265–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Heath JL, Burgett SE, Gaca AM, Jaffe R, Wechsler DS. Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy. Pediatr Blood Cancer. 2014;61(10):1874–6.

    PubMed  Google Scholar 

  66. Iwabuchi H, Kawashima H, Umezu H, Takachi T, Imamura M, Saitoh A, et al. Successful treatment of histiocytic sarcoma with cladribine and high-dose cytosine arabinoside in a child. Int J Hematol. 2017;106(2):299–303.

    PubMed  Google Scholar 

  67. Tomlin J, Orosco RK, Boles S, Tipps A, Wang HY, Husseman J, et al. Successful treatment of multifocal histiocytic sarcoma occurring after renal transplantation with cladribine, high-dose cytarabine, G-CSF, and mitoxantrone (CLAG-M) followed by allogeneic hematopoietic stem cell transplantation. Case Rep Hematol. 2015;2015: 728260.

    PubMed  PubMed Central  Google Scholar 

  68. Idbaih A, Mokhtari K, Emile JF, Galanaud D, Belaid H, de Bernard S, et al. Dramatic response of a BRAF V600E-mutated primary CNS histiocytic sarcoma to vemurafenib. Neurology. 2014;83(16):1478–80.

    PubMed  Google Scholar 

  69. Branco B, Comont T, Ysebaert L, Picard M, Laurent C, Oberic L. Targeted therapy of BRAF V600E-mutant histiocytic sarcoma: a case report and review of the literature. Eur J Haematol. 2019;103(4):444–8.

    PubMed  Google Scholar 

  70. Mourah S, Lorillon G, Meignin V, Vercellino L, de Margerie-Mellon C, Pages C, et al. Dramatic transient improvement of metastatic BRAF(V600E)-mutated Langerhans cell sarcoma under treatment with dabrafenib. Blood. 2015;126(24):2649–52.

    CAS  PubMed  Google Scholar 

  71. Bailey KM, Castle VP, Hummel JM, Piert M, Moyer J, McAllister-Lucas LM. Thalidomide therapy for aggressive histiocytic lesions in the pediatric population. J Pediatr Hematol Oncol. 2012;34(6):480–3.

    CAS  PubMed  Google Scholar 

  72. Shukla N, Kobos R, Renaud T, Teruya-Feldstein J, Price A, McAllister-Lucas L, et al. Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab. Cancer. 2012;118(15):3719–24.

    CAS  PubMed  Google Scholar 

  73. May JM, Waddle MR, Miller DH, Stross WC, Kaleem TA, May BC, et al. Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review. Radiat Oncol. 2018;13(1):167.

    PubMed  PubMed Central  Google Scholar 

  74. Kieran MW, Geoerger B, Dunkel IJ, Broniscer A, Hargrave D, Hingorani P, et al. A phase I and pharmacokinetic study of oral dabrafenib in children and adolescent patients with recurrent or refractory. Clin Cancer Res. 2019;25(24):7294–302.

    CAS  PubMed  Google Scholar 

  75. Rosen LS, LoRusso P, Ma WW, Goldman JW, Weise A, Colevas AD, et al. A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors. Invest New Drugs. 2016;34(5):604–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Papo M, Diamond EL, Cohen-Aubart F, Emile JF, Roos-Weil D, Gupta N, et al. High prevalence of myeloid neoplasms in adults with non-Langerhans cell histiocytosis. Blood. 2017;130(8):1007–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Yang Y, Wang D, Cui L, Ma HH, Zhang L, Lian HY, et al. Effectiveness and safety of dabrafenib in the treatment of 20 Chinese children with BRAFV600E-mutated Langerhans cell histiocytosis. Cancer Res Treat. 2021;53(1):261–9.

    CAS  PubMed  Google Scholar 

  78. Váradi Z, Bánusz R, Csomor J, Kállay K, Varga E, Kertész G, et al. Effective BRAF inhibitor vemurafenib therapy in a 2-year-old patient with sequentially diagnosed Langerhans cell histiocytosis and Erdheim-Chester disease. Onco Targets Ther. 2017;10:521–6.

    PubMed  PubMed Central  Google Scholar 

  79. Bhatia A, Ulaner G, Rampal R, Hyman DM, Abdel-Wahab O, Durham BH, et al. Single-agent dabrafenib for. Haematologica. 2018;103(4):e177–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Cohen Aubart F, Emile JF, Maksud P, Galanaud D, Cluzel P, Benameur N, et al. Efficacy of the MEK inhibitor cobimetinib for wild-type BRAF Erdheim-Chester disease. Br J Haematol. 2018;180(1):150–3.

    PubMed  Google Scholar 

  81. Di Liso E, Pennelli N, Lodovichetti G, Ghiotto C, Dei Tos AP, Conte P, et al. Braf mutation in interdigitating dendritic cell sarcoma: a case report and review of the literature. Cancer Biol Ther. 2015;16(8):1128–35.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Hematology/Oncology, Western University and Children’s Hospital London Health Sciences Centre, London, ON, Canada

    Ashley V. Geerlinks

  2. Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Oussama Abla

Authors
  1. Ashley V. Geerlinks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oussama Abla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashley V. Geerlinks.

Ethics declarations

Funding

No financial assistance was used to conduct the review or assist with the preparation of this article.

Conflicts of Interest/Competing Interests

Ashley V. Geerlinks and Oussama Abla have no conflicts of interest that might be directly relevant to the content of this article.

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Availability of Data and Material

Not applicable.

Code Availability

Not applicable.

Authors’ Contributions

AVG and OA contributed to the literature review and writing of the manuscript.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Geerlinks, A.V., Abla, O. Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors. Pediatr Drugs 25, 399–409 (2023). https://doi.org/10.1007/s40272-023-00569-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-023-00569-8

Search

Navigation