@article{3106938,
    title = "A case of Alemtuzumab-induced neutropenia in multiple sclerosis in association with the expansion of large granular lymphocytes",
    author = "Vakrakou, A.G. and Tzanetakos, D. and Valsami, S. and Grigoriou, E. and Psarra, K. and Tzartos, J. and Anagnostouli, M. and Andreadou, E. and Evangelopoulos, M.E. and Koutsis, G. and Chrysovitsanou, C. and Gialafos, E. and Dimitrakopoulos, A. and Stefanis, L. and Kilidireas, C.",
    journal = "BMC Neurology",
    year = "2018",
    volume = "18",
    number = "1",
    publisher = "BioMed Central Ltd.",
    issn = "1471-2377",
    doi = "10.1186/s12883-018-1183-4",
    keywords = "alemtuzumab;  glatiramer;  natalizumab;  prednisolone;  alemtuzumab;  immunologic factor;  monoclonal antibody, adult;  Article;  blood smear;  case report;  CD3+ CD8+ T lymphocyte;  clinical article;  corticosteroid therapy;  disease association;  disease duration;  disease exacerbation;  drug dose reduction;  drug substitution;  drug withdrawal;  Expanded Disability Status Scale;  female;  flow cytometry;  follow up;  human;  immunophenotyping;  JC virus;  large granular lymphocyte;  leukocyte count;  multiple sclerosis;  neurologic disease;  neurologic examination;  neutropenia;  optic neuritis;  remission;  T lymphocyte;  treatment duration;  treatment outcome;  chemically induced;  lymphocyte;  multiple sclerosis;  neutropenia;  pathology, Adult;  Alemtuzumab;  Antibodies, Monoclonal, Humanized;  Female;  Humans;  Immunologic Factors;  Lymphocytes;  Multiple Sclerosis, Relapsing-Remitting;  Neutropenia",
    abstract = "Background: Alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in Multiple Sclerosis (MS) patients compared to β-interferon. It acts against CD52, leading primarily to lymphopenia. Recent data have shown that mild neutropenia is observed in 16% of treated MS-patients whereas severe neutropenia occurred in 0.6%. Case presentation: Herein, we present the case of a 34-year-old woman with relapsing-remitting MS, with a history of treatment with glatiramer acetate and natalizumab, who subsequently received Alemtuzumab (12 mg / 24 h × 5 days). 70-days after the last Alemtuzumab administration, the patient displayed neutropenia (500 neutrophils/μL) with virtual absence of B-cells (0.6% of total lymphocytes), low values of CD4-T-cells (6.6%) and predominance of CD8-T-cells (48%) and NK-cells (47%); while large granular lymphocytes (LGL) predominated in the blood-smear examination. Due to prolonged neutropenia (5-days) the patient was placed on low-dose corticosteroids leading to sustained remission. Conclusion: This is the first case of a patient with relapsing-remitting MS with neutropenia two months post-Alemtuzumab, with simultaneous presence of LGL cells in the blood and a robust therapeutic response to prednisolone. We recommend testing with a complete blood count every 15 days in the first 3 months after the 1st Alemtuzumab administration and searching for large granular lymphocytes cell expansion on microscopic examination of the peripheral blood if neutropenia develops. © 2018 The Author(s)."
}