Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar;54(3):416-23.
doi: 10.1002/pbc.22326.

Neurodegenerative central nervous system Langerhans cell histiocytosis and coincident hydrocephalus treated with vincristine/cytosine arabinoside

Carl E Allen  1 , Ricardo Flores, Ronald Rauch, Robert Dauser, Jeffrey C Murray, Diane Puccetti, David A Hsu, Paul Sondel, Maxine Hetherington, Stan Goldman, Kenneth L McClain
Affiliations

Neurodegenerative central nervous system Langerhans cell histiocytosis and coincident hydrocephalus treated with vincristine/cytosine arabinoside

Carl E Allen et al. Pediatr Blood Cancer. 2010 Mar.

Abstract

Background: Central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) include mass lesions and a neurodegenerative (ND) syndrome with ataxia, dysarthria, dysmetria, learning and behavior difficulties and/or characteristic changes on brain MRIs. Hydrocephalus has rarely been reported in LCH. LCH lesions of the orbit, mastoid and temporal bones ("CNS-Risk" lesions) and diabetes insipidus predispose patients to ND-CNS-LCH. Treatment options have been limited and only a case series using trans-retinoic acid (ATRA) and intravenous immunoglobulin (IVIG) have been published.

Methods: We have used cytosine arabinoside (ARA-C) with or without vincristine to treat eight patients with ND-CNS LCH.

Patients: Seven male children and one young adult male with clinical and radiologic ND-CNS-LCH were treated with a regimen of vincristine 1.5 mg/m(2) on day 1 and ARA-C 100 mg/m(2) daily for 5 days or ARA-C alone monthly for 4-19 months. Seven patients were evaluated with an ataxia rating scale (ARS) and all with serial MRIs of the brain.

Results: Five of seven patients had decreases in their ARS scores and/or decreased T2 hyperintense lesions on MRI images. Grade 2 neutropenia was the most frequent adverse event. Vincristine-associated neuropathy occurred in two patients. Hydrocephalus caused symptoms and signs that confounded the diagnosis and management of ND-CNS-LCH in all four patients affected with both.

Conclusions: Subtle changes in neurologic function may be complicated by hydrocephalus. Vcr/ARA-C or ARA-C were an effective therapies for some ND-CNS LCH patients. A clinical trial using this and possibly other modalities such as IVIG or ATRA should be done.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Statement. Dr. McClain owns shares of Johnson and Johnson common stock. None of the other authors have any conflicts of interest.

Figures

Fig. 1
Fig. 1
Fig. 2
Fig. 2
Handwriting samples of Patient 1. A. Before treatment with vincristine/cytosine arabinoside. B: After 2 months of treatment.
Fig. 3
Fig. 3
Fig. 4
Fig. 4
Fig. 5
Fig. 5
Fig. 6
Fig. 6
Fig. 7
Fig. 7
See this image and copyright information in PMC

Comment in

  • VCR/AraC chemotherapy and ND-CNS-LCH.
    Imashuku S, Shioda Y, Tsunematsu Y, Imamura T, Morimoto A; Japan LCH Study Group. Imashuku S, et al. Pediatr Blood Cancer. 2010 Jul 15;55(1):215-6. doi: 10.1002/pbc.22478. Pediatr Blood Cancer. 2010. PMID: 20310001 No abstract available.

References

    1. Grois N, Favara BE, Mostbeck GH, Prayer D. Central Nervous System Disease in Langerhans Cell Histiocytosis. In: Egeler RM, D’Angio GJ, editors. Hematology/Oncology Clinics of North America: Langerhans Cell Histiocytosis. Vol. 12. Philidelphia: W.B. Sunders Company; 1998. pp. 287–305. - PubMed
    1. Prayer D, Grois N, Prosch H, et al. MR imaging presentation of intracranial disease associated with Langerhans cell histiocytosis. AJNR Am J Neuroradiol. 2004;25:880–91. - PMC - PubMed
    1. Grois N, Potschger U, Prosch H, et al. Risk factors for diabetes insipidus in Langerhans cell histiocytosis. Pediatr Blood Cancer. 2006;46:228–33. - PubMed
    1. Mittheisz E, Seidl R, Prayer D, et al. Central nervous system-related permanent consequences in patients with Langerhans cell histiocytosis. Pediatr Blood Cancer. 2007;48:50–6. - PubMed
    1. Ganong WF. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clinical and experimental pharmacology & physiology. 2000;27:422–7. - PubMed

MeSH terms