TY - JOUR
T1 - Rituximab (anti-CD20) adjunctive therapy for Opsoclonus-Myoclonus syndrome
AU - Pranzatelli, Michael R.
AU - Tate, Elizabeth D.
AU - Travelstead, Anna L.
AU - Barbosa, Jerry
AU - Bergamini, Robert A.
AU - Civitello, Lucy
AU - Franz, David N.
AU - Greffe, Brian S.
AU - Hanson, Robin D.
AU - Hurwitz, Craig A.
AU - Kalinyak, Karen A.
AU - Kelfer, Howard
AU - Khakoo, Yasmin
AU - Mantovani, John F.
AU - Nicholson, Stacy H.
AU - Sanders, Joann M.
AU - Wegner, Stephen
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
KW - B lymphocytes
KW - B-cell trafficking
KW - CSF immunophenotyping
KW - Corticotropin
KW - Dancing eyes
KW - IVIg
KW - Kinsbourne syndrome
KW - Neuroblastoma
KW - Paraneoplastic syndrome
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U2 - 10.1097/01.mph.0000212991.64435.f0
DO - 10.1097/01.mph.0000212991.64435.f0
M3 - Article
C2 - 17006265
AN - SCOPUS:33749358285
SN - 1077-4114
VL - 28
SP - 585
EP - 593
JO - Journal of Pediatric Hematology/Oncology
JF - Journal of Pediatric Hematology/Oncology
IS - 9
ER -