title: Reconstitution of circulating lymphocyte counts in FTY720-treated MS patients.
abstract: FTY720 (Fingolimod) reduces multiple sclerosis disease activity by inducing lymphopenia and inhibiting lymphocyte re-entry from lymph nodes. Peripheral lymphocyte reconstitution following drug discontinuation has been considered relatively rapid (2-4 weeks), based on short-term studies. We investigated the kinetics of lymphocyte reconstitution in MS patients in open label extension phases of FTY720 clinical trials who discontinued therapy after prolonged use (>1-5 years), and examined histological features of a mediastinal lymph node obtained from a lymphopenic FTY720 patient. Although three patients showed reconstitution of peripheral lymphocytes within the predicted timeline, two patients continued to be lymphopenic 9 and 34 months after therapy cessation. Lymph nodes from the latter patient showed preserved architecture. Notwithstanding preserved lymph node integrity, time for lymphocyte reconstitution after prolonged FTY720 therapy can be significantly greater than predicted by shorter-term studies. This is relevant for clinical decisions regarding management of patients using this therapy and for introducing alternate therapies.
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Trina A
authors.initials: TA
authors.lastname: Johnson
authors.forename: Igor
authors.initials: I
authors.lastname: Shames
authors.forename: Mark
authors.initials: M
authors.lastname: Keezer
authors.forename: Yves
authors.initials: Y
authors.lastname: Lapierre
authors.forename: David G
authors.initials: DG
authors.lastname: Haegert
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Jack
authors.initials: J
authors.lastname: Antel
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood; D005260:Female; D000068876:Fingolimod Hydrochloride; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008198:Lymph Nodes / Q000166:cytology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008231:Lymphopenia / Q000139:chemically induced; D008482:Mediastinum / Q000033:anatomy & histology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D010352:Patient Dropouts; D011409:Propylene Glycols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D054400:Receptors, CCR7 / Q000378:metabolism; D013110:Sphingosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D028761:Withholding Treatment
chemical_list: C515370:CCR7 protein, human; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D054400:Receptors, CCR7; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine