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

Texas Children's Cancer Center/Hematology Service, Houston, TX 77030, USA.
Pediatric Blood & Cancer (Impact Factor: 2.39). 03/2010; 54(3):416-23. DOI: 10.1002/pbc.22326
Source: PubMed


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.
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.
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.
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.

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Available from: Kenneth Louis Mcclain, Mar 04, 2015
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    • "Cytarabine with or without Vincristine provided improvement in 5/8 patients of which 4/8 remained stable over more than 7 years of follow-up and one relapsed but is improved after treatment with intravenous Methotrexate. Patients who responded to Cytarabine/Vincristine had symptoms for less than 18 months before starting treatment [60,61]. Thus early onset of Cytarabine is recommended as first line therapy, but for any case of neurodegenerative LCH we suggest discussion with the reference centre for your country (Grade C1). "
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