title: Clinical relevance of differential lymphocyte recovery after alemtuzumab therapy for multiple sclerosis.
abstract: OBJECTIVE
  Alemtuzumab is potentially a highly effective treatment for relapsing multiple sclerosis (MS) acting via complement-mediated lysis of circulating lymphocytes. Variability in posttreatment lymphocyte recovery time is observed, with some patients showing striking durability in the efficacy of treatment. This study aims to establish whether this observed variation affects clinical and imaging parameters of disease activity.
  
  
  METHODS
  A total of 56 patients were followed for a median of 39.5 months post alemtuzumab treatment with interval clinical assessments, lymphocyte immunophenotyping, and MRI. Timing and degree of CD4+, CD8+, and CD19+ recovery were correlated with the re-emergence of disease activity defined as clinical relapse, increasing disability, and new T2/enhancing lesions on MRI.
  
  
  RESULTS
  New disease activity was recorded in 14% of patients. Mean time to CD19+, CD8+, and CD4+ reconstitution was 6, 10, and 36 months. No differences were observed in CD8+ and CD19+ reconstitution between patients with active disease and those in remission. Patients with active disease showed an accelerated recovery of CD4+ cells (p = 0.001) with a difference in absolute CD4+ counts at 24 months (p = 0.009). CD4+ counts <388.5 × 10(6) cells/mL predicted MRI stability.
  
  
  CONCLUSIONS
  Differential lymphocyte recovery in MS following alemtuzumab may be a biomarker for relapse and also inform monitoring and treatment protocols.
  
  
  METHODS
  This study provides Class IV evidence that differential lymphocyte reconstitution after alemtuzumab treatment may be a biomarker for relapse.
authors.affiliation: Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, Cardiff, UK.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Cossburn
authors.forename: Katharine
authors.initials: K
authors.lastname: Harding
authors.forename: Gillian
authors.initials: G
authors.lastname: Ingram
authors.forename: Tariq
authors.initials: T
authors.lastname: El-Shanawany
authors.forename: Adrian
authors.initials: A
authors.lastname: Heaps
authors.forename: Trevor P
authors.initials: TP
authors.lastname: Pickersgill
authors.forename: Stephen
authors.initials: S
authors.lastname: Jolles
authors.forename: Neil P
authors.initials: NP
authors.lastname: Robertson
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000187:drug effects*; D018791:CD4 Lymphocyte Count / Q000706:statistics & numerical data; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D016130:Immunophenotyping / Q000379:methods / Q000706:statistics & numerical data*; D018655:Lymphocyte Count / Q000706:statistics & numerical data*; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D059906:Neuroimaging / Q000379:methods / Q000706:statistics & numerical data; D012008:Recurrence; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19; D000074323:Alemtuzumab