Neurodegenerative Central Nervous System Langerhans Cell Histiocytosis and Coincident Hydrocephalus Treated With Vincristine/Cytosine Arabinoside

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. Pediatr Blood Cancer 2010;54:416-423. (C) 2009 Wiley-Liss, Inc.