Aktualisierte AWMF Leitlinie zur Diagnostik und Therapie der Langerhanszell Histiozytose (LCH) im Kindes- und Jugendalter

Zusammenfassung

Die Langerhanszell Histiozytose (LCH) ist eine seltene neoplastische Erkrankung, die vor allem im Kindes- und Jugendalter auftritt. Die Erkrankung kann prinzipiell jedes Organ befallen, weswegen sehr unterschiedliche klinische Erscheinungsbilder möglich sind. Der klinische Verlauf der LCH reicht von einer Spontanheilung bis hin zu einem rasch progredienten tödlichen Verlauf. Die Ausbreitungsdiagnostik bestimmt das Vorgehen. Manche Patienten qualifizieren sich für eine watch-and-wait Strategie, während andere einer Chemotherapie mit den Standardmedikamenten Vinblastin und Prednison bedürfen. Durch die Identifizierung von Mutationen im MAPK-Signalweg wächst das Interesse an zielgerichteten Medikamenten wie den BRAF-Inhibitoren. Chronisch-rezidivierende Verläufe und Spätschäden sind ein weiteres Problem der Erkrankung und stehen im Mittelpunkt derzeitiger Forschungsaktivitäten.

Abstract

Langerhans cell Histiocytosis is a rare neoplastic disease, which occurs mainly in children and adolescents. The disease may affect any organ, and therefore, the clinical symptoms vary widely. Some patients have a spontaneous remission of the disease, whereas others experience a rapid and potentially lethal clinical course. The therapeutic approach depends on the extent of the disease, and reaches from a watch-and-wait strategy to chemotherapy with the standard drugs vinblastine and prednisone. The identification of mutations in the MAPK-pathway resulted in growing interest in targeted therapy using compounds such as the BRAF inhibitors. Chronic relapses and permanent sequelae are important problems of LCH and are the focus of current research.

Schlüsselwörter

Leitlinie - Langerhanszell Histiozytose - Kind - Therapie

Key words

guideline - Langerhans cell histiozytosis - child - therapy

Publication History

Article published online:
04 September 2023

• Literatur

• 1 Rodriguez-Galindo C, Allen CE. Langerhans cell histiocytosis. Blood 2020; 135: 1319-1331
• 2 Perrone A, Lakatos K, Pegoraro F. et al. Whole-body magnetic resonance imaging for staging Langerhans cell histiocytosis in children and young adults. Pediatr Blood Cancer 2022; e30064
• 3 Kim JR, Yoon HM, Jung AY. et al. Comparison of whole-body MRI, bone scan, and radiographic skeletal survey for lesion detection and risk stratification of Langerhans Cell Histiocytosis. Sci Rep 2019; 9: 317
• 4 Donadieu J, Rolon MA, Thomas C. et al. Endocrine involvement in pediatric-onset Langerhans' cell histiocytosis: a population-based study. J Pediatr 2004; 144: 344-350
• 5 Grois N, Potschger U, Prosch H. et al. Risk factors for diabetes insipidus in langerhans cell histiocytosis. Pediatr Blood Cancer 2006; 46: 228-233
• 6 Haupt R, Nanduri V, Calevo MG. et al. Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatr Blood Cancer 2004; 42: 438-444
• 7 Minkov M, Grois N, Heitger A. et al. Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Med Pediatr Oncol 2002; 39: 581-585
• 8 Simko SJ, Tran HD, Jones J. 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: 479-487
• 9 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: 1415-1423
• 10 Kudo K, Maeda M, Suzuki N. et al. Nationwide retrospective review of hematopoietic stem cell transplantation in children with refractory Langerhans cell histiocytosis. Int J Hematol 2020; 111: 137-148
• 11 Donadieu J, Larabi IA, Tardieu M. et al. Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study. J Clin Oncol 2019; 37: 2857-2865
• 12 Eckstein OS, Visser J, Rodriguez-Galindo C. et al. Clinical responses and persistent BRAF V600E(+) blood cells in children with LCH treated with MAPK pathway inhibition. Blood. 2019; 133: 1691-1694
• 13 Allen CE, Ladisch S, McClain KL. How I treat Langerhans cell histiocytosis. Blood. 2015; 126: 26-35
• 14 Dhir A, Kelly DR, Watts RG. et al. Recurrent Skin Langerhan Cell Histiocytosis Successfully Treated With Indomethacin Monotherapy. J Pediatr Hematol Oncol 2020; 42: e795-e797
• 15 Yule SM, Hamilton JRL, Windebank KP. Recurrent pneumomediastinum and pneumothorax in Langerhans cell histiocytosis. Medical and Pediatric Oncology 1997; 29: 139-142
• 16 Simko SJ, McClain KL, Allen CE. Up-front therapy for LCH: is it time to test an alternative to vinblastine/prednisone?. British Journal of Haematology 2015; 169: 299-301
• 17 Eckstein OS, Nuchtern JG, Mallory GB. et al. Management of severe pulmonary Langerhans cell histiocytosis in children. Pediatr Pulmonol 2020; 55: 2074-2081
• 18 De Benedittis D, Mohamed S, Rizzo L. et al. Indomethacin is an effective treatment in adults and children with bone Langerhans cell histiocytosis (LCH). Br J Haematol 2020; 191: e109-e113
• 19 Morimoto A, Shioda Y, Imamura T. et al. Nationwide survey of bisphosphonate therapy for children with reactivated Langerhans cell histiocytosis in Japan. Pediatr Blood Cancer 2011; 56: 110-115
• 20 Barnbrock A, Hutter C, Bochennek K. et al. Therapiestrategien bei Kindern und Jugendlichen mit Langerhanszell Histiozytosen. Klin Päd 2023;
• 21 Sakamoto K, Morimoto A, Shioda Y. et al. Long-term complications in uniformly treated paediatric Langerhans histiocytosis patients disclosed by 12 years of follow-up of the JLSG-96/02 studies. Br J Haematol 2021; 192: 615-620
• 22 Cohen Aubart F, Idbaih A, Emile JF. et al. Histiocytosis and the nervous system: from diagnosis to targeted therapies. Neuro Oncol 2021; 23: 1433-1446
• 23 Sveijer M, von Bahr Greenwood T, Jadersten M. et al. Screening for neurodegeneration in Langerhans cell histiocytosis with neurofilament light in plasma. Br J Haematol 2022; 198: 721-728
• 24 Bagnasco F, Zimmermann SY, Egeler RM. et al. Langerhans cell histiocytosis and associated malignancies: A retrospective analysis of 270 patients. Eur J Cancer 2022; 172: 138-145