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

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Abstract
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.