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J Pediatr Hematol Oncol ; 28(9): 585-93, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17006265

RESUMO

PURPOSE: To determine if rituximab, an anti-CD20 monoclonal antibody, reduces cerebrospinal fluid (CSF) B-cell expansion in opsoclonus-myoclonus syndrome (OMS) and results in clinical improvement. METHODS: Sixteen children with OMS and increased % CD20 B-cells in CSF received 4 rituximab infusions (375 mg/m IV) as add-on therapy to corticotropin (ACTH), intravenous immunoglobulins, or both, and were reevaluated 6 months later. Outcome measures were clinical (motor function, behavior, sleep) and immunologic (CSF and blood immunophenotype and Ig levels). Controls were 16 age-matched and sex-matched children, who did not have OMS. RESULTS: After rituximab, 81% of OMS had a lower motor severity score, and 44% improved one severity category. Mean total score decreased by 44% (P = 0.0005). Rituximab reduced rage score, nighttime awakenings, and the number of children with opsoclonus, action myoclonus, drooling, gait ataxia, and rage. Despite a 51% reduction in ACTH dose, 9 of 11 children on ACTH did not relapse. The percentage of CSF CD19 (and CD20) B-cells was lowered in all children (undetectable in 6), with a 90% reduction in the group mean (P = 0.00003). CSF B-cells were no longer expanded compared with controls. In blood, CD19 B-cells decreased (-90%, P = 0.0003), as did the CSF:blood CD19 B-cell ratio (P = 0.00003). Serum IgM fell by 69% (below reference range), with no statistically significant change in IgG or IgA. CONCLUSIONS: Rituximab seems efficacious and safe as adjunctive therapy for OMS. Selective targeting of CSF B lymphocytes represents a novel and valuable paradigm shift in the therapy for centrally mediated paraneoplastic disorders.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndromes Paraneoplásicas do Sistema Nervoso/líquido cefalorraquidiano , Síndromes Paraneoplásicas do Sistema Nervoso/tratamento farmacológico , Anticorpos Monoclonais Murinos , Linfócitos B/efeitos dos fármacos , Comportamento/efeitos dos fármacos , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/efeitos dos fármacos , Líquido Cefalorraquidiano/imunologia , Quimioterapia Adjuvante , Feminino , Citometria de Fluxo , Humanos , Imunoterapia , Lactente , Masculino , Atividade Motora/efeitos dos fármacos , Neuroblastoma/complicações , Neuroblastoma/tratamento farmacológico , Rituximab , Sono/efeitos dos fármacos
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