The effect of cyclophosphamide on T lymphocytes and T lymphocyte subsets in patients with chronic progressive multiple sclerosis

Moderate doses of cyclophosphamide can cause effects on lymphocytes that may last for some time after discontinuation of the treatment. Since cyclophosphamide is also often used at high doses, we studied the short- and long-term effects of such a high dose (8 grams in 20 days) in 50 patients with chronic progressive multiple sclerosis with the use of monoclonal antibodies. The treatment caused a depletion of lymphocytes, especially CD4+ cells resulting in a significant decrease of the CD4/CD8 ratio. These changes can still be found up to 13.5 years after treatment. Although there was some recovery in the first few years after treatment this was only partial. Therefore, some of the effects of high dose cyclophosphamide on cellular immunity may be permanent. These changes should be taken into account when studying immune parameters or considering new treatments in these patients.

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“…This confirms earlier reports (19,20,10). The effect of CY is more pronounced on CD4' cells resulting in a decrease of the CD4+/CD8+ ratio.…”

Section: Discussionsupporting

confidence: 94%

Long-lasting effects of cyclophosphamide on lymphocytes in peripheral blood and spinal fluid

Uitdehaag

Nillesen

Hommes

1989

Acta Neurologica Scandinavica

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“…Cyclophosphamide was one of the first drugs shown to reverse the course of EAE even when given after symptoms appeared (18,19) and provided a rationale for treating patients with MS. Early studies on the immunologic effects of cyclophosphamide demonstrated a decrease in the absolute number of T cells (20), a reduction in circulating B cells (21), a decrease in the synthesis of IgG within the blood-brain barrier (22), and decreased spontaneous proliferation of lymphocytes (23). We have investigated the use of pulse cyclophosphamide to treat progressive MS and found a positive clinical effect in younger patients with actively progressive disease of short duration (24,25), although not all studies of cyclophosphamide therapy found a positive effect (26).…”

Section: Introductionmentioning

confidence: 99%

Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy.

et al. 1998

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“…Cyclophosphamide effectively reduces the number of circulating T and B cells, 25,26 in addition to creating a more favorable cytokine balance, shifting away from autoimmune Th1 responses and reductions in interleukin 12 (IL-12) and interferon gamma (IFN-γ). 27 Cyclophosphamide and its metabolites are also capable of penetrating the blood–brain barrier and can exert direct intrathecal immunologic effects.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclophosphamide has a long history in the treatment of MS, having been utilized in some of the first published treatment trials in this condition, 23,24 although at much lower doses than in this study. Cyclophosphamide effectively reduces the number of circulating T and B cells, 25,26 in addition to creating a more favorable cytokine balance, shifting away from autoimmune Th1 responses and reductions in interleukin 12 (IL-12) and interferon gamma (IFN-γ). 27 Cyclophosphamide and its metabolites are also capable of penetrating the blood–brain barrier and can exert direct intrathecal immunologic effects.…”

Section: Discussionmentioning

confidence: 99%

Treatment of relapsing–remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance

et al. 2011

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Background Previous studies have described stabilization of aggressive multiple sclerosis (MS) with one-time induction therapy with high-dose cyclophosphamide (HiCy). The long-term benefit of this stabilization followed by conventional therapy has not been explored. Objective The objective of this study was to evaluate the safety and clinical outcomes following treatment of relapsing–remitting MS with HiCy induction therapy followed by glatiramer acetate maintenance. Methods A retrospective review of a closely followed population of thirty two MS patients treated with HiCy (200mg/kg intravenous infusion over 4 days) followed by maintenance with glatiramer acetate was performed. Results Annualized relapse rate was reduced from 1.37 in the 2 years prior to treatment to 0.27 over a mean post-treatment follow-up period of 14 months (range 0.5–33.8). The projected probability of relapse-free survival at 2 years was 0.64 (95% CI 0.37–0.82). The projected probability of Expanded Disability Status Scale (EDSS) progression-free survival at 2 years was 0.77 (95% CI 0.43–0.92). The mean number of gadolinium-enhanced lesions was reduced from 0.86 (SD 1.6) at baseline to 0 at 12 months and 0.08 (SD 0.28) at 15–24 months. A total of 55% of patients had no evidence of disease activity in follow-up. Infectious complications occurred in 47% with no long-term morbidity and no deaths. Conclusions Induction therapy with HiCy followed by long-term maintenance with glatiramer acetate is well tolerated in patients with MS, and appears to be efficacious in reducing the risk of relapse, disability progression, and new MRI lesions.

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The effect of cyclophosphamide on T lymphocytes and T lymphocyte subsets in patients with chronic progressive multiple sclerosis

Cited by 29 publications

References 12 publications

Long-lasting effects of cyclophosphamide on lymphocytes in peripheral blood and spinal fluid

Long-lasting effects of cyclophosphamide on lymphocytes in peripheral blood and spinal fluid

Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy.

Treatment of relapsing–remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance

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