CD 4 + CD 62L + cells: A monitoring marker of fingolimod dosage in multiple sclerosis

Objectives Fingolimod ( FTY ) potentially inhibits the disease activity of multiple sclerosis ( MS ), but induces severe lymphocytopenia that might be related viral infections, including progressive multifocal leukoencephalopathy. We use a reduced dosage of FTY treatment to avoid its cessation because of lymphocytopenia. FTY inhibits the egress of CD 62L + cells from lymph nodes, and the number of CD 4 + CD 62L + cells, a major population of CD 62L + cells, in blood is a maker to evaluate the strength of FTY action in patients with MS treated by intermittent drug holidays of FTY . Methods A total of 24 Japanese patients with MS were treated with variable dosages of FTY initially based on the number of lymphocytes, and then changed to CD 4 + CD 62L + cell counts as a marker. Fluorescence‐activated cell sorting analysis was used to evaluate the number of CD 4 + CD 62L + cells in fresh blood of 21 MS patients treated with FTY for 30–94 months, including the mean period of 27.5 months of daily administration. Results The CD 4 + CD 62L + cell counts and the proportion of patients with <2% CD 4 + CD 62L + cells in total lymphocytes declined from 12 ± 13 cells/mm 3 (median 8 cells/mm 3 ) to 31 ± 4 cells/mm 3 (median 27 cells/mm 3 ) and 61.5% to 0%, respectively, after further dosage reduction. Their annual relapse rates were kept to <0.03, even after inducing CD 4 + CD 62L+ counts as a monitoring marker. The target range of CD 4 + CD 62L + cells on reduction of FTY dosage was 10–80 cells/mm 3 . Conclusions It is critical to monitor CD 4 + CD 62L + cells rather than total lymphocyte count to avoid excessive FTY administration.