Michael R Pranzatelli1, Elizabeth D Tate2, Nathan R McGee3, Craig A MacArthur4. 1. National Pediatric Myoclonus Center and National Pediatric Neuroinflammation Organization, Inc, Orlando, Florida. Electronic address: mpranzatelli@omsusa.org. 2. National Pediatric Myoclonus Center and National Pediatric Neuroinflammation Organization, Inc, Orlando, Florida. Electronic address: etate@omsusa.org. 3. National Pediatric Myoclonus Center and National Pediatric Neuroinflammation Organization, Inc, Orlando, Florida. Electronic address: mcgee6510@att.net. 4. Department of Pediatric Hematology/Oncology, Golisano Children's Hospital of Southwest Florida, Lee Memorial Health Care System, Fort Myers, Florida. Electronic address: craig.macarthur@leehealth.org.
Abstract
BACKGROUND: Rituximab (anti-CD20) has been used as B-cell-targeted intervention to treat opsoclonus-myoclonus syndrome. Due to isolated reports of chronic hypogammaglobulinemia and B lymphopenia following rituximab in several disorders, and rapid B-cell depletion after a few doses, we reduced the dosage 20% in our clinical practice. METHODS: In this Institutional Review Board-approved retrospective study, 32 children with opsoclonus-myoclonus syndrome and cerebrospinal fluid B-cell expansion had received front-loaded adrenocorticotropic hormone, intravenous immunoglobulin, and rituximab combination immunotherapy for de novo opsoclonus-myoclonus syndrome. Parametric statistical analysis compared 10 children receiving 1200 mg/m2 of rituximab (300 mg/m2 × 4) and 22 receiving 1500 mg/m2 (375 mg/m2 × 4). Clinical response had been video documented and scored by a blinded observer. RESULTS: In both groups, motor severity (total score) lessened by ≥76% and cerebrospinal fluid B cells were similarly depleted (≥95%) six months after treatment. None of the treated patients remained unable to walk independently. Serum IgM depletion was analogous in the 1200 mg/m2 (-73%) and 1500 mg/m2 group (-64%). The relapse frequency was similar in both groups. Side effects were principally steroidal, tolerable, and transient. Circulating B-cell repopulation was comparable. CONCLUSIONS: The reduced-dose of rituximab in rituximab combination immunotherapy was as effective and well tolerated as the standard dose, and provided rapid, early therapeutic intervention in opsoclonus-myoclonus syndrome. Pending a long-term prospective study, these are proof-of-concept data in support of challenging the dose of rituximab in various disorders, which may have different dose requirements.
BACKGROUND:Rituximab (anti-CD20) has been used as B-cell-targeted intervention to treat opsoclonus-myoclonus syndrome. Due to isolated reports of chronic hypogammaglobulinemia and B lymphopenia following rituximab in several disorders, and rapid B-cell depletion after a few doses, we reduced the dosage 20% in our clinical practice. METHODS: In this Institutional Review Board-approved retrospective study, 32 children with opsoclonus-myoclonus syndrome and cerebrospinal fluid B-cell expansion had received front-loaded adrenocorticotropic hormone, intravenous immunoglobulin, and rituximab combination immunotherapy for de novo opsoclonus-myoclonus syndrome. Parametric statistical analysis compared 10 children receiving 1200 mg/m2 of rituximab (300 mg/m2 × 4) and 22 receiving 1500 mg/m2 (375 mg/m2 × 4). Clinical response had been video documented and scored by a blinded observer. RESULTS: In both groups, motor severity (total score) lessened by ≥76% and cerebrospinal fluid B cells were similarly depleted (≥95%) six months after treatment. None of the treated patients remained unable to walk independently. Serum IgM depletion was analogous in the 1200 mg/m2 (-73%) and 1500 mg/m2 group (-64%). The relapse frequency was similar in both groups. Side effects were principally steroidal, tolerable, and transient. Circulating B-cell repopulation was comparable. CONCLUSIONS: The reduced-dose of rituximab in rituximab combination immunotherapy was as effective and well tolerated as the standard dose, and provided rapid, early therapeutic intervention in opsoclonus-myoclonus syndrome. Pending a long-term prospective study, these are proof-of-concept data in support of challenging the dose of rituximab in various disorders, which may have different dose requirements.