Advances in cyclophosphamide treatment of multiple sclerosis: criteria, designs, safety
Keywords:
cyclophosphamide, multiple sclerosis, effects of treatment, safetyAbstract
Cyclophosphamide (CTX) has mixed effect in multiple sclerosis (MS) patients on clinical status and on active changes visualized by the brain MRI. Selection criteria for CTX therapy comprise younger age (18–40 years), relapses in the year prior to therapy, less than 2 years in the progressive phase or malignant course, the presence of contrast-enhancing lesions or new T2-related lesions and unresponsiveness to 1 year immunomodulation or to 6 months mitoxantrone treatment. Among 7 cohorts of aggressive relapsing-remitting MS or deteriorating moderate to severe secondary progressive MS CTX treatment decreased disability score in 5 and reduced relapse rate in 2. The improvement lasted on average 2 years. Four MRI investigations showed the transient decrease of contrast-enhancing lesions and 3 studies documented the stable number of T2-related lesions up to 24 months. Eight treatment protocols for CTX therapy in MS include inter alia low-dose immunosuppression, induction, high-dose pulse therapy, combination or subsequent maintenance treatment with IFN beta or glatiramer acetate. The adverse but mostly reversible effects of CTX are numerous: leucopenia (90%), nausea or vomiting (63%), alopecia (54%), infections (36%), menstrual disorders and infertility (21%), bladder pathology (8%). Toxic effects should be carefully monitored and prevented.
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