Pranzatelli Michael R, Tate Elizabeth D, Travelstead Anna L, Barbosa Jerry, Bergamini Robert A, Civitello Lucy, Franz David N, Greffe Brian S, Hanson Robin D, Hurwitz Craig A, Kalinyak Karen A, Kelfer Howard, Khakoo Yasmin, Mantovani John F, Nicholson Stacy H, Sanders Joann M, Wegner Stephen
National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, Springfield, IL, USA.
J Pediatr Hematol Oncol. 2006 Sep;28(9):585-93. doi: 10.1097/01.mph.0000212991.64435.f0.
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.
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.
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.
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.
确定抗CD20单克隆抗体利妥昔单抗是否能减少眼阵挛-肌阵挛综合征（OMS）患者脑脊液（CSF）中B细胞的扩增并带来临床改善。
16例CSF中CD20+B细胞百分比升高的OMS患儿接受4次利妥昔单抗静脉输注（375mg/m²），作为促肾上腺皮质激素（ACTH）、静脉注射免疫球蛋白或两者联合治疗的附加疗法，并在6个月后进行重新评估。观察指标包括临床指标（运动功能、行为、睡眠）和免疫指标（CSF和血液免疫表型及免疫球蛋白水平）。对照组为16例年龄和性别匹配、无OMS的儿童。
使用利妥昔单抗后，81%的OMS患儿运动严重程度评分降低，44%改善了一个严重程度等级。平均总分下降了44%（P = 0.0005）。利妥昔单抗降低了愤怒评分、夜间觉醒次数，以及患有眼阵挛、动作性肌阵挛、流涎、步态共济失调和愤怒的患儿数量。尽管ACTH剂量降低了51%，但11例接受ACTH治疗的患儿中有9例未复发。所有患儿CSF中CD19（和CD20）B细胞的百分比均降低（6例检测不到），组均值降低了90%（P = 0.00003）。与对照组相比，CSF中的B细胞不再扩增。血液中，CD19 B细胞减少（-90%，P = 0.
