B cell depletion therapy for new-onset opsoclonus-myoclonus.
Twelve immunotherapy-naïve children with opsoclonus-myoclonus syndrome and CSF B cell expansion received rituximab, adrenocorticotropic hormone (ACTH), and IVIg. Motor severity lessened 73% by 6 mo and 81% at 1 yr (P < 0.0001). Opsoclonus and action myoclonus disappeared rapidly, whereas gait ataxia and some other motor components improved more slowly. ACTH dose was tapered by 87%. Reduction in total CSF B cells was profound at 6 mo (-93%). By study end, peripheral B cells returned to 53% of baseline and serum IgM levels to 63%. Overall clinical response trailed peripheral B cell and IgM depletion, but improvement continued after their levels recovered. All but one non-ambulatory subject became ambulatory without additional chemotherapy; two relapsed and remitted; four had rituximab-related or possibly related adverse events; and two had low-titer human anti-chimeric antibody. Combination of rituximab with conventional agents as initial therapy was effective and safe. A controlled trial with long-term safety monitoring is indicated.
Pranzatelli
Michael R
MR
National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9643, USA. mpranzatelli@siumed.edu
Tate
Elizabeth D
ED
Swan
Jennifer A
JA
Travelstead
Anna L
AL
Colliver
Jerry A
JA
Verhulst
Steven J
SJ
Crosley
Carl J
CJ
Graf
William D
WD
Joseph
Suja A
SA
Kelfer
Howard M
HM
Raju
G Praveen
GP
D000324:Adrenocorticotropic Hormone / Q000009:adverse effects / Q000627:therapeutic use; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001259:Ataxia / Q000188:drug therapy; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000009:adverse effects / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D009207:Myoclonus / Q000188:drug therapy; D053578:Opsoclonus-Myoclonus Syndrome / Q000503:physiopathology / Q000628:therapy*; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007155:Immunologic Factors; D000069283:Rituximab; D000324:Adrenocorticotropic Hormone