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First-Line Treatment of Pediatric Langerhans Cell Histiocytosis

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Histiocytic Disorders

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Abstract

The current first-line treatment strategies in pediatric Langerhans cell histiocytosis (LCH) are based on extent of disease at diagnosis and early response to treatment. For limited forms of disease, such as single-bone lesions and isolated skin LCH, a wait-and-watch strategy is advised after the diagnosis has been made; other forms of treatment, including local and systemic therapies, may also be considered in some circumstances. For more extensive forms of LCH, systemic therapy is indicated. The treatment backbones most often used are those of vinblastine and corticosteroids, or cytarabine and corticosteroids. In multifocal bone LCH, the optimal treatment duration has not been established yet. For multisystem LCH, it has become clear that early intensification in unresponsive disease is very important. Prolongation of maintenance treatment to a year has resulted in a decrease in the reactivation rates. The effect of further prolongation is being studied in the current LCH-IV protocol of the Histiocyte Society. It is to be expected that in the (near) future, the use of BRAF and MEK inhibitors may be introduced in first-line therapy, especially for very high-risk patients. For these and other patients, recently identified risk factors need to be validated in ongoing and future trials, and new risk factors need to be identified. This should subsequently allow for the development of more refined risk-adapted treatment strategies.

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Abbreviations

2-CdA:

Cladribine

6-MP:

6-Mercaptopurine

AIEOP :

Associazione Italiana Ematologia Oncologia Pediatrica

ARA-C:

Cytarabine

BRAF:

Gene encoding for B-Raf protein (serine/threonine protein kinase B-Raf)

BRAF-V600E :

Mutation of BRAF gene with substitution of glutamate for valine at amino acid position 600

CNS:

Central nervous system

ctDNA:

Circulating tumor DNA

CXCR-4:

CXC chemokine receptor type 4

DAL-HX:

Deutsche Arbeitsgemeinschaft für Leukämieforschung und –Behandlung im Kindesalter e.V. – Histiozytose X

DI:

Diabetes insipidus

DNA:

Deoxyribonucleic acid

EFS:

Event-free survival

JLSG:

Japan Langerhans Cell Histiocytosis Study Group

LCH:

Langerhans Cell Histiocytosis

MEK:

Gene encoding for mitogen-activated protein kinase kinase

MRI:

Magnetic resonance imaging

MS-LCH:

Multisystem Langerhans Cell Histiocytosis

MTX:

Methotrexate

NAD:

Non-active disease

ND-CNS LCH:

Neurodegenerative central nervous system LCH

PDN:

Prednisone

POG:

Pediatric Oncology Group

PUVA:

Psoralen plus ultraviolet A

RO:

Risk organ

VBL:

Vinblastine

VCR:

Vincristine

VP-16:

Etoposide

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Authors and Affiliations

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

    Carlos Rodriguez-Galindo MD

  2. Emma Children’s Hospital/Academic Medical Center, Department of Pediatric Oncology, Amsterdam, The Netherlands

    Cor van den Bos MD, PhD.

Authors
  1. Carlos Rodriguez-Galindo MD
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  2. Cor van den Bos MD, PhD.
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Correspondence to Cor van den Bos MD, PhD. .

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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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Rodriguez-Galindo, C., van den Bos, C. (2018). First-Line Treatment of Pediatric Langerhans Cell Histiocytosis. In: Abla, O., Janka, G. (eds) Histiocytic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-59632-7_5

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