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鞘内注射氨丁三醇脂质体预防非霍奇金淋巴瘤患者神经并发症。

Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

机构信息

Department of Neurology and Neurosurgery, Clínica Universidad de Navarra, Avda. Pío XII, 36, Pamplona 31008, Spain.

出版信息

J Neurooncol. 2011 Jul;103(3):603-9. doi: 10.1007/s11060-010-0428-x. Epub 2010 Oct 17.

Abstract

Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

摘要

中枢神经系统 (CNS) 预防是治疗非霍奇金淋巴瘤 (NHL) 亚型的必要措施,这些亚型有较高的 CNS 受累风险。鞘内 (IT) 脂质体阿糖胞苷,一种半衰期延长的制剂,已被证明在治疗高级别淋巴瘤患者的脑膜疾病中是安全有效的。我们回顾性分析了 2007 年 4 月至 2009 年 5 月在我们机构接受预防性 IT 脂质体阿糖胞苷治疗且发生神经系统并发症的所有成人高级别 NHL 患者。我们记录了入院信息、化疗方案、临床特征、神经影像学、脑脊液、神经生理学数据和结局。神经毒性根据国家癌症研究所常见毒性标准 (NCI-CTC) 进行分级。14 例患者中有 4 例 (28%) 在接受中位数为 3.5 个 IT 疗程的脂质体阿糖胞苷后出现中度或重度神经毒性 (NCI-CTC 的 2 级和 3 级),表现为圆锥马尾综合征或假性脑瘤样综合征。所有患者均接受皮质类固醇预防蛛网膜炎。即使同时给予皮质类固醇,鞘内给予脂质体阿糖胞苷也会导致一些患者出现显著的神经毒性。我们讨论了这些影响的潜在发病机制,并提出了假设的治疗措施来预防这些并发症。在为高级别 NHL 患者预防性给予 IT 脂质体阿糖胞苷时,专家应注意这些可能的并发症,应进行更多的前瞻性研究以更清楚地阐明这些并发症的频率和特征。

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