Treatment of Relapsed and Refractory Langerhans Cell Histiocytosis in Children

  • Oussama Abla
  • Carlos Rodriguez-Galindo
  • Paul Veys


Approximately 50% of patients with multisystem (MS) Langerhans cell histiocytosis (LCH) are refractory to initial treatment or develop reactivation of their disease within 5 years, and the treatment of these patients has been a challenge and their outcome is very poor. Treatment failures in patients with low-risk LCH are not associated with mortality but with morbidity, and their optimal treatment is not well defined. Nucleoside analogues such as cladribine and clofarabine have an excellent activity in treating resistant MS-LCH, and patients with very high-risk LCH despite multiple salvage therapies can be possibly cured with haematopoietic stem cell transplant. BRAF-V600E inhibitors, such as vemurafenib and dabrafenib, have proven to be effective in relapsed/refractory MS-LCH. However, larger studies are needed to define the best dose and duration of these drugs and to better identify the toxicity profile in children with LCH. The effect of these drugs on future reactivations and late sequelae needs to be well defined, as well. Future trials will most likely examine the combination of BRAF or BRAF/MEK inhibitors with chemotherapy in relapsed/refractory MS patients.


Relapsed LCH Treatment Nucleoside analogues HSCT Targeted therapies 


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Oussama Abla
    • 1
  • Carlos Rodriguez-Galindo
    • 2
  • Paul Veys
    • 3
  1. 1.Department of Pediatrics, Division of Hematology/OncologyHospital for Sick Children, University of TorontoTorontoCanada
  2. 2.Departments of Global Pediatric Medicine and Oncology, St. Jude Children’s Research HospitalMemphisUSA
  3. 3.Blood and Bone Marrow Transplantation Unit, Great Ormond Street Hospital for ChildrenLondonUK

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