靶向细胞内抗原的副肿瘤神经综合征的细胞免疫抑制。

Dana Orange, Mayu Frank, Suyan Tian, Athanasios Dousmanis, Ronen Marmur, Noreen Buckley, Salina Parveen, Jerome J Graber, Nathalie Blachère, Robert B Darnell
{"title":"靶向细胞内抗原的副肿瘤神经综合征的细胞免疫抑制。","authors":"Dana Orange,&nbsp;Mayu Frank,&nbsp;Suyan Tian,&nbsp;Athanasios Dousmanis,&nbsp;Ronen Marmur,&nbsp;Noreen Buckley,&nbsp;Salina Parveen,&nbsp;Jerome J Graber,&nbsp;Nathalie Blachère,&nbsp;Robert B Darnell","doi":"10.1001/archneurol.2012.595","DOIUrl":null,"url":null,"abstract":"<p><p>BACKGROUND Tumor treatment is the mainstay of therapy for paraneoplastic neurologic disorders (PNDs), but it is only effective in some cases and other treatment options are limited. OBJECTIVE To evaluate the short-term use of a combination of prednisone and tacrolimus for acute neurologic worsening in PND in which intracellular antigens are targeted. DESIGN Retrospective single-center case series of patients with PND treated with tacrolimus. SETTING The Rockefeller University Hospital, a research hospital in New York, New York. PATIENTS Twenty-six patients with PND with high titer (≥1:1000) anti-HuD, anti-Yo, or anti-CRMP5 autoantibodies were enrolled. Patients were referred from Memorial Sloan Kettering Cancer Center or self-referred. Two patients discontinued intervention owing to adverse events. INTERVENTIONS Patients were treated with tacrolimus, 0.15-0.30 mg/kg per day, in 2 divided oral doses with 60 mg per day of oral prednisone, tapered off during 1 to 4 weeks. MAIN OUTCOME MEASURES The primary outcome measure was median survival. Neurologic examinations before and after treatment as well as adverse events are described. RESULTS Median survival time was 52 months from time of diagnosis. Some patients experienced neurologic improvement that was functionally meaningful. The incidence of adverse events was similar to that generally reported with tacrolimus. CONCLUSIONS A short course of prednisone and tacrolimus to target central nervous system T cells in patients with PND with acute neurologic decline in which intracellular antigens are targeted was well tolerated and warrants further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00378326.</p>","PeriodicalId":8321,"journal":{"name":"Archives of neurology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1001/archneurol.2012.595","citationCount":"39","resultStr":"{\"title\":\"Cellular immune suppression in paraneoplastic neurologic syndromes targeting intracellular antigens.\",\"authors\":\"Dana Orange,&nbsp;Mayu Frank,&nbsp;Suyan Tian,&nbsp;Athanasios Dousmanis,&nbsp;Ronen Marmur,&nbsp;Noreen Buckley,&nbsp;Salina Parveen,&nbsp;Jerome J Graber,&nbsp;Nathalie Blachère,&nbsp;Robert B Darnell\",\"doi\":\"10.1001/archneurol.2012.595\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BACKGROUND Tumor treatment is the mainstay of therapy for paraneoplastic neurologic disorders (PNDs), but it is only effective in some cases and other treatment options are limited. OBJECTIVE To evaluate the short-term use of a combination of prednisone and tacrolimus for acute neurologic worsening in PND in which intracellular antigens are targeted. DESIGN Retrospective single-center case series of patients with PND treated with tacrolimus. SETTING The Rockefeller University Hospital, a research hospital in New York, New York. PATIENTS Twenty-six patients with PND with high titer (≥1:1000) anti-HuD, anti-Yo, or anti-CRMP5 autoantibodies were enrolled. Patients were referred from Memorial Sloan Kettering Cancer Center or self-referred. Two patients discontinued intervention owing to adverse events. INTERVENTIONS Patients were treated with tacrolimus, 0.15-0.30 mg/kg per day, in 2 divided oral doses with 60 mg per day of oral prednisone, tapered off during 1 to 4 weeks. MAIN OUTCOME MEASURES The primary outcome measure was median survival. Neurologic examinations before and after treatment as well as adverse events are described. RESULTS Median survival time was 52 months from time of diagnosis. Some patients experienced neurologic improvement that was functionally meaningful. The incidence of adverse events was similar to that generally reported with tacrolimus. CONCLUSIONS A short course of prednisone and tacrolimus to target central nervous system T cells in patients with PND with acute neurologic decline in which intracellular antigens are targeted was well tolerated and warrants further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00378326.</p>\",\"PeriodicalId\":8321,\"journal\":{\"name\":\"Archives of neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2012-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1001/archneurol.2012.595\",\"citationCount\":\"39\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of neurology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1001/archneurol.2012.595\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1001/archneurol.2012.595","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 39

摘要

肿瘤治疗是副肿瘤神经系统疾病(PNDs)的主要治疗方法,但仅在某些情况下有效,其他治疗选择有限。目的:评价强的松联合他克莫司治疗以细胞内抗原为靶点的PND急性神经系统恶化的短期疗效。设计:他克莫司治疗的PND患者回顾性单中心病例系列。洛克菲勒大学医院,位于纽约的一家研究型医院。患者26例PND患者具有高滴度(≥1:1000)抗hud、抗yo或抗crmp5自身抗体。患者从纪念斯隆凯特琳癌症中心转介或自行转介。2例患者因不良事件停止干预。干预措施:患者接受他克莫司治疗,0.15-0.30 mg/kg /天,分2次口服剂量,外加60 mg/天的口服强的松,1 - 4周逐渐减少。主要结局指标主要结局指标为中位生存期。描述了治疗前后的神经系统检查以及不良事件。结果中位生存时间为52个月。一些患者的神经功能得到了有意义的改善。不良事件的发生率与一般报道的他克莫司相似。结论:短疗程的泼尼松和他克莫司靶向中枢神经系统T细胞治疗伴有急性神经功能衰退的PND患者细胞内抗原的耐受性良好,值得进一步研究。试验注册clinicaltrials.gov标识符:NCT00378326。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cellular immune suppression in paraneoplastic neurologic syndromes targeting intracellular antigens.

BACKGROUND Tumor treatment is the mainstay of therapy for paraneoplastic neurologic disorders (PNDs), but it is only effective in some cases and other treatment options are limited. OBJECTIVE To evaluate the short-term use of a combination of prednisone and tacrolimus for acute neurologic worsening in PND in which intracellular antigens are targeted. DESIGN Retrospective single-center case series of patients with PND treated with tacrolimus. SETTING The Rockefeller University Hospital, a research hospital in New York, New York. PATIENTS Twenty-six patients with PND with high titer (≥1:1000) anti-HuD, anti-Yo, or anti-CRMP5 autoantibodies were enrolled. Patients were referred from Memorial Sloan Kettering Cancer Center or self-referred. Two patients discontinued intervention owing to adverse events. INTERVENTIONS Patients were treated with tacrolimus, 0.15-0.30 mg/kg per day, in 2 divided oral doses with 60 mg per day of oral prednisone, tapered off during 1 to 4 weeks. MAIN OUTCOME MEASURES The primary outcome measure was median survival. Neurologic examinations before and after treatment as well as adverse events are described. RESULTS Median survival time was 52 months from time of diagnosis. Some patients experienced neurologic improvement that was functionally meaningful. The incidence of adverse events was similar to that generally reported with tacrolimus. CONCLUSIONS A short course of prednisone and tacrolimus to target central nervous system T cells in patients with PND with acute neurologic decline in which intracellular antigens are targeted was well tolerated and warrants further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00378326.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Archives of neurology
Archives of neurology 医学-临床神经学
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信