Rituximab (anti-CD20) adjunctive therapy for Opsoclonus-Myoclonus syndrome Journal Article
| Authors: | Pranzatelli, M. R.; Tate, E. D.; Travelstead, A. L.; Barbosa, J.; Bergamini, R. A.; Civitello, L.; Franz, D. N.; Greffe, B. S.; Hanson, R. D.; Hurwitz, C. A.; Kalinyak, K. A.; Kelfer, H.; Khakoo, Y.; Mantovani, J. F.; Nicholson, S. H.; Sanders, J. M.; Wegner, S. |
| Article Title: | Rituximab (anti-CD20) adjunctive therapy for Opsoclonus-Myoclonus syndrome |
| Abstract: | 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. Copyright © 2006 by Lippincott Williams & Wilkins. |
| Keywords: | child; clinical article; chemotherapy, adjuvant; rituximab; flow cytometry; outcome assessment; infection; relapse; aciclovir; immunoglobulin; b lymphocyte; b-lymphocytes; monoclonal antibody; injection site reaction; antibodies, monoclonal; disease severity; statistical significance; immunotherapy; immunoglobulin g; cerebrospinal fluid; infant; neuroblastoma; blood analysis; scoring system; drug infusion; behavior; immunophenotyping; virus infection; immunologic factors; myoclonus; motor performance; motor activity; paraneoplastic syndrome; neurologic disease; ataxia; cd19 antigen; chickenpox; urticaria; immunoglobulin m; diphenhydramine; immunoglobulin a; sleep; behavioral science; corticotropin; opsoclonus myoclonus syndrome; arousal; hypersalivation; cd20 antibody; b lymphocytes; b-cell trafficking; csf immunophenotyping; dancing eyes; ivig; kinsbourne syndrome; rage; paraneoplastic syndromes, nervous system |
| Journal Title: | Journal of Pediatric Hematology/Oncology |
| Volume: | 28 |
| Issue: | 9 |
| ISSN: | 1077-4114 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2006-09-01 |
| Start Page: | 585 |
| End Page: | 593 |
| Language: | English |
| DOI: | 10.1097/01.mph.0000212991.64435.f0 |
| PUBMED: | 17006265 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 52" - "Export Date: 4 June 2012" - "CODEN: JPHOF" - "Source: Scopus" |
