Perini Paola, Calabrese Massimiliano, Rinaldi Luciano, Gallo Paolo
Multiple Sclerosis Centre Veneto Region, First Neurology Clinic, University Hospital, Padova, Italy.
Expert Opin Drug Saf. 2007 Mar;6(2):183-90. doi: 10.1517/14740338.6.2.183.
Cyclophosphamide (Cyc) is an alkylating agent used to treat malignancies and autoimmune diseases, such as lupus nephritis, rheumatoid arthritis and immune-mediated neuropathies. Over the past 40 years, Cyc has also been applied to treat multiple sclerosis (MS) and the effective stabilisation of rapidly progressive forms of MS has been demonstrated in several studies. Cyc has a dose-dependent bimodal effect on the immune system. High doses have been demonstrated to induce an anti-inflammatory immune deviation (i.e., suppression of T helper 1 and enhancement of T helper 2 activity), affect CD4CD25(high) regulatory T cells and establish a state of marked immunosuppression. Data from the literature suggest that Cyc is particularly indicated in the treatment of young MS patients, suffering from a very active inflammatory disease characterised by frequent relapses and rapid accumulation of disability and displaying gadolinium-enhancing lesions on brain magnetic resonance. The most common Cyc-based therapeutic protocol applied in MS consists of monthly intravenous pulses for 1 year followed by bimonthly pulses for the second year, with or without prior infusion of corticosteroids. This protocol is usually well tolerated by the patients. Indeed, most of the side effects (mild alopecia, nausea and vomiting, cystitis) are dose dependent, transient and completely reversible. Definitive amenorrhoea is observed only in older female patients (aged > 40 years). Cyc has a safety and efficacy profile similar to that of mitoxantrone and can be used in patients whose disease is not controlled by IFN-beta or glatiramer acetate. Short course (6-12 months) of Cyc therapy can precede the initiation of immunomodulatory treatment in selected patients with an aggressive MS onset.
环磷酰胺（Cyc）是一种烷化剂，用于治疗恶性肿瘤和自身免疫性疾病，如狼疮性肾炎、类风湿性关节炎和免疫介导的神经病变。在过去40年中，Cyc也被用于治疗多发性硬化症（MS），并且多项研究已证明其对快速进展型MS有有效的稳定作用。Cyc对免疫系统具有剂量依赖性的双峰效应。高剂量已被证明可诱导抗炎性免疫偏差（即抑制辅助性T细胞1并增强辅助性T细胞2活性），影响CD4CD25（高）调节性T细胞并建立显著的免疫抑制状态。文献数据表明，Cyc特别适用于治疗年轻的MS患者，这些患者患有非常活跃的炎性疾病，其特征为频繁复发、残疾迅速累积且脑磁共振成像显示钆增强病变。MS中最常用的基于Cyc的治疗方案包括第一年每月静脉注射脉冲治疗，随后第二年每两个月进行一次脉冲治疗，无论是否预先输注皮质类固醇。该方案通常患者耐受性良好。事实上，大多数副作用（轻度脱发、恶心和呕吐、膀胱炎）是剂量依赖性的、短暂的且完全可逆的。仅在年龄较大的女性患者（年龄>40岁）中观察到永久性闭经。Cyc的安全性和有效性与米托蒽醌相似，可用于疾病不受β-干扰素或醋酸格拉替雷控制的患者。在选定的具有侵袭性MS发病的患者中，可在开始免疫调节治疗之前先进行短期（6 - 12个月）的Cyc治疗。
