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Awad A et al. – Cyclophosphamide (CYC), an alkylating agent, penetrates the blood–brain barrier and CNS parenchyma well. However, while CYC has been used in clinical trials and off–label in clinical practice in patients with MS for over three decades, data on its efficacy in very heterogeneous groups of study patients have been conflicting. New myeloablative treatment paradigms with CYC may provide a therapeutic option in patients that do not respond to other agents. In this article the authors review the scientific rationale that led to the initial clinical trials with CYC. The authors will also outline the safety, tolerability and efficacy of CYC and provide neurologists with guidelines for its use in patients with MS and other inflammatory disorders of the CNS, including neuromyelitis optica (NMO). Finally, an outlook into relatively novel treatment approaches is provided.

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