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Treatment of Relapsed and Refractory Langerhans Cell Histiocytosis in Children

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Histiocytic Disorders

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Abstract

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.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Oussama Abla MD

  2. Departments of Global Pediatric Medicine and Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Carlos Rodriguez-Galindo MD

  3. Blood and Bone Marrow Transplantation Unit, Great Ormond Street Hospital for Children, London, UK

    Paul Veys MBBS FRCP FRCPath FRCPCH

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  1. Oussama Abla MD
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  2. Carlos Rodriguez-Galindo MD
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  3. Paul Veys MBBS FRCP FRCPath FRCPCH
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Correspondence to Oussama Abla MD .

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Editors and Affiliations

  1. University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada

    Oussama Abla

  2. Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany

    Gritta Janka

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Abla, O., Rodriguez-Galindo, C., Veys, P. (2018). Treatment of Relapsed and Refractory Langerhans Cell Histiocytosis in Children. In: Abla, O., Janka, G. (eds) Histiocytic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-59632-7_6

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