RT Journal Article
SR Electronic
T1 Clinical relevance of differential lymphocyte recovery after alemtuzumab therapy for multiple sclerosis
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 55
OP 61
DO 10.1212/WNL.0b013e31827b5927
VO 80
IS 1
A1 Cossburn, Mark D.
A1 Harding, Katharine
A1 Ingram, Gillian
A1 El-Shanawany, Tariq
A1 Heaps, Adrian
A1 Pickersgill, Trevor P.
A1 Jolles, Stephen
A1 Robertson, Neil P.
YR 2013
UL http://n.neurology.org/content/80/1/55.abstract
AB 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 × 106 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.Classification of evidence: This study provides Class IV evidence that differential lymphocyte reconstitution after alemtuzumab treatment may be a biomarker for relapse.AID=autoimmune disease; CBC=complete blood count; EDSS=Expanded Disability Status Scale; LLN=lower limit of laboratory-based normal ranges; MS=multiple sclerosis; T-regs=regulatory T cells