Langerhans-Cell Histiocytosis In Children: A Bicentric Study From Tunisia

Authors

  • Samia Rekaia Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Manel Gouja Pediatric Hematology Department at the Bone Marrow Center Tunis, Tunisia
  • Feten Fedhila Children's Medicine Department A at the Bechir Hamza Children's Hospital, Tunis, Faculty of medicine of Tunis, University of Tunis El Manar, Tunisia
  • Ilhem Ben Fradj Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Samar Rhayem Children's Medicine Department A at the Bechir Hamza Children's Hospital, Tunis, Faculty of medicine of Tunis, University of Tunis El Manar, Tunisia
  • Ghofrane Bedoui Pediatric Hematology Department at the Bone Marrow Center Tunis, Tunisia
  • Aicha Bettaieb Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Ameni Merdassi Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Hajer Ben Belgacem Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Fethi Mellouli Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Mohamed Bejaoui Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Monia Khemiri Children's Medicine Department A at the Bechir Hamza Children's Hospital, Tunis, Faculty of medicine of Tunis, University of Tunis El Manar, Tunisia
  • Monia Ben Khaled Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia
  • Monia Ouederni Pediatric Hematology Department at the Bone Marrow Center Tunis , Faculty of medicine, University of Tunis El Manar ,Tunisia

DOI:

https://doi.org/10.62438/tunismed.v104i07.6763

Keywords:

Pediatric, Langerhans cell histiocytosis, overall survival, disease-free survival, LCH reactivation

Abstract

Langerhans cell histiocytosis (LCH) is the most common form of histiocytosis in children, characterized by clonal proliferation of CD1a+ and CD207+ dendritic cells. This retrospective study aimed to evaluate the clinical characteristics, treatment response, and progression of LCH in children diagnosed between January 2010 and July 2023 at two Tunisian referral centers. Forty-three patients were enrolled with a median age at diagnosis of 3 years. Multisystem LCH with risk organs involvement was the most common group (44%), followed by single-system LCH (37%). Bone, skin, and liver were the most frequently affected organs. Central nervous system tumorous lesions were observed in five patients. The BRAF-V600E mutation was identified in eight of nine tested cases. Thirty-four patients received a vinblastine-based first-line therapy; six patients (18%) showed no response after two courses of vinblastine induction. Two patients received a combination of Cytarabine and Cladribine, with a favorable outcome in one case. BRAF inhibitors were used in four cases, with a favorable response in two. Reactivations occurred in 28% of patients, and 23% experienced at least one permanent consequence. Overall survival (OS) and disease-free survival (DFS) rates were 93% and 63%, respectively. Risk organs involvement and poor response to vinblastine induction were associated with worse outcomes.

Downloads

Download data is not yet available.

References

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 Jun 2;127(22):2672–81. doi:10.1182/blood-2016-01-690636 PubMed

PMID: 26966089; PubMed Central PMCID: PMC5161007.

Rodriguez-Galindo C, Allen CE. Langerhans cell histiocytosis. Blood. 2020 Apr 16;135(16):1319–31. doi:10.1182/blood.2019000934 3. Haupt R, Minkov M, Astigarraga I, Schäfer E, Nanduri V, Jubran R, et al. Langerhans Cell Histiocytosis (LCH): Guidelines for Diagnosis,

Clinical Work-Up, and Treatment for Patients Till the Age of 18 Years. Pediatr Blood Cancer. 2013 Feb;60(2):175–84. doi:10.1002/

pbc.24367 PubMed PMID: 23109216; PubMed Central PMCID: PMC4557042.

Pnds_hl_has_15112021revue_litterature.pdf [Internet]. [cited 2024 Jun 26]. Available from: https://www.has-sante.fr/upload/

docs/application/pdf/2021-11/pnds_hl_has_15112021revue_ litterature.pdf

Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, et al. Improved outcome in multisystem Langerhans cell histiocytosis

is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556–62. doi:10.1182/blood-2007-08-106211

Minkov M, Steiner M, Pötschger U, Aricò M, Braier J, Donadieu J, et al. Reactivations in Multisystem Langerhans Cell Histiocytosis: Data

of the International LCH Registry. The Journal of Pediatrics. 2008 Nov;153(5):700-705.e2. doi:10.1016/j.jpeds.2008.05.002

Abla O. Langerhans cell histiocytosis: promises and caveats of targeted therapies in high-risk and CNS disease. Hematology

Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):386–95. doi:10.1182/hematology.2023000439 PubMed PMID: 38066856;

PubMed Central PMCID: PMC10726990.

Rigaud C, Barkaoui MA, Thomas C, Bertrand Y, Lambilliotte A, Miron J, et al. Langerhans cell histiocytosis: therapeutic strategy and

outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age. British Journal of Haematology. 2016;174(6):887–98.

doi:10.1111/bjh.14140

Rodriguez-Galindo C. Clinical features and treatment of Langerhans cell histiocytosis. Acta Paediatrica. 2021 Nov;110(11):2892–902.

doi:10.1111/apa.16014

Thacker N, Abla O. Pediatric Langerhans cell histiocytosis: state of the science and future directions. Clinical advances in hematology

& oncology : H&O. 2019 Feb 1;17:122–31.

Héritier S, Barkaoui MA, Miron J, Thomas C, Moshous D, Lambilliotte A, et al. Incidence and risk factors for clinical neurodegenerative

Langerhans cell histiocytosis: a longitudinal cohort study. British Journal of Haematology. 2018;183(4):608–17. doi:10.1111/

bjh.15577

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 Jun 20;121(25):5006–14. doi:10.1182/blood-2012-09-455774

PNDS HL 2021 vCRMR 15112021.pdf [Internet]. [cited 2024 Jun 26]. Available from: http://www.histiocytose.org/medias/PNDS%20

HL%202021%20vCRMR%2015112021.pdf

Tzotzola V, Petrikkos L, Papadakis V, Mitropoulou G, Kelaidi C, Dimitriadis E, et al. Long-term outcome, clinical course and

treatment approaches of paediatric langerhans cell histiocytosis: A greek reference centre report. Acta Paediatr. 2021 Jun;110(6):1944–

doi:10.1111/apa.15743 PubMed PMID: 33382132.

Liu H, Stiller CA, Crooks CJ, Rous B, Bythell M, Broggio J, et al. Incidence, prevalence and survival in patients with Langerhans cell

histiocytosis: A national registry study from England, 2013–2019. Br J Haematol. 2022 Dec;199(5):728–38. doi:10.1111/bjh.18459

PubMed PMID: 36122574; PubMed Central PMCID: PMC9826274.

Allen CE, Merad M, McClain KL. Langerhans-Cell Histiocytosis. N Engl J Med. 2018 Aug 30;379(9):856–68. doi:10.1056/NEJMra1607548

PubMed PMID: 30157397; PubMed Central PMCID: PMC6334777.

Morimoto A, Shioda Y, Imamura T, Kudo K, Kawaguchi H, Sakashita K, et al. Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study. International Journal of Hematology. 2016 Apr 4;104. doi:10.1007/

s12185-016-1993-3

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 Nov 1;37(31):2857–65. doi:10.1200/JCO.19.00456

PubMed PMID: 31513482; PubMed Central PMCID: PMC6823889.

Bahabri A, Abla O. Advances in our understanding of genetic markers and targeted therapies for pediatric LCH. Expert Rev

Hematol. 2024 Jun;17(6):223–31. doi:10.1080/17474086.2024.23 53772 PubMed PMID: 38721670.

Lei J, Wang W, Lin D, Zhu C, Jia W, Weng W, et al. Vemurafenib combined with chemotherapy achieved sustained remission in

pediatric LCH: a multi-center observational study. J Cancer Res Clin Oncol. 2024 Jan 17;150(1):12. doi:10.1007/s00432-023-05551-y

Eckstein OS, Visser J, Rodriguez-Galindo C, Allen CE, NACHO-LIBRE Study Group. Clinical responses and persistent BRAF V600E+

blood cells in children with LCH treated with MAPK pathway inhibition. Blood. 2019 Apr 11;133(15):1691–4. doi:10.1182/

blood-2018-10-878363 PubMed PMID: 30718231; PubMed Central PMCID: PMC6460419.

Cohen Aubart F, Idbaih A, Emile JF, Amoura Z, Abdel-Wahab O, Durham BH, et al. Histiocytosis and the nervous system:

from diagnosis to targeted therapies. Neuro Oncol. 2021 May 16;23(9):1433–46. doi:10.1093/neuonc/noab107 PubMed PMID:

; PubMed Central PMCID: PMC8408883.

Additional Files

Published

2026-07-12

Issue

Vol. 104 No. 07 (2026): Tunis Med Jul 2026

Section

Original articles

Categories

License

Copyright (c) 2026 La Tunisie Médicale

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.