Fabian Sierra Morales1,2, Igor J Koralnik1,2, Shiva Gautam3, Soleil Samaan1, Jacob A Sloane4. 1. Division of Neuro-Immunology, Department of Neurology, Beth Israel Deaconess Medical Center, Multiple Sclerosis Center, Harvard Medical School, 330 Brookline Ave, Ks212, Boston, MA, 02115, USA. 2. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 3. Division of Biostatistics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 4. Division of Neuro-Immunology, Department of Neurology, Beth Israel Deaconess Medical Center, Multiple Sclerosis Center, Harvard Medical School, 330 Brookline Ave, Ks212, Boston, MA, 02115, USA. jsloane@bidmc.harvard.edu.
Abstract
OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and characterize its impact on T lymphocyte subsets in MS patients. METHODS: We performed a retrospective analysis of 194 RRMS patients treated with DMF at the Beth Israel Deaconess Medical Center (BIDMC) over a median of 17 months. We reviewed demographics, ethnic background, prior medication history, complete blood counts and T lymphocyte subsets. Possible lymphopenia risk factors examined included age, prior natalizumab exposure, vitamin D levels, and concomitant exposure to carbamazepine, opiates, tobacco, or steroids. Lymphopenia was defined as grade 1: absolute lymphocytes count (ALC) 800-999/μl; grade 2: ALC 500-799/μl; grade 3: ALC 200-499/μl; and grade 4: ALC < 200/μl. RESULTS: Of 194 DMF-treated patients, 73 (38%) developed lymphopenia and reached an ALC nadir after a median of 504 days (range 82-932). Risk of developing DMF-induced lymphopenia increased with BMI 25-30, older age, white ethnicity, non-smoking status, and lowest quartile baseline ALC. Prior exposure to natalizumab or concomitant steroid, opiates or carbamazepine/oxcarbamazepine use was not associated with lymphopenia. Compared to baseline levels, CD8 T cells were significantly more reduced than CD4 cells. CD8 counts were more commonly reduced with age or white ethnicity. Subjects with BMI 25-30 was associated with a higher risk of abnormal CD4 cell count reductions. In contrast, non-smokers were more likely to experience reductions in both CD4 and CD8 counts while on DMF. CONCLUSIONS: Patients with low baseline lymphocyte counts, with intermediate BMI, with white ethnicity, with advanced age, or with no tobacco use, had a significantly higher incidence of lymphopenia on DMF. Intermediate BMI or lowest quartile baseline ALC predicted low CD4 levels, while advanced age or white ethnicity predicted low CD8 levels from DMF exposure.
OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and characterize its impact on T lymphocyte subsets in MSpatients. METHODS: We performed a retrospective analysis of 194 RRMS patients treated with DMF at the Beth Israel Deaconess Medical Center (BIDMC) over a median of 17 months. We reviewed demographics, ethnic background, prior medication history, complete blood counts and T lymphocyte subsets. Possible lymphopenia risk factors examined included age, prior natalizumab exposure, vitamin D levels, and concomitant exposure to carbamazepine, opiates, tobacco, or steroids. Lymphopenia was defined as grade 1: absolute lymphocytes count (ALC) 800-999/μl; grade 2: ALC 500-799/μl; grade 3: ALC 200-499/μl; and grade 4: ALC < 200/μl. RESULTS: Of 194 DMF-treated patients, 73 (38%) developed lymphopenia and reached an ALC nadir after a median of 504 days (range 82-932). Risk of developing DMF-induced lymphopenia increased with BMI 25-30, older age, white ethnicity, non-smoking status, and lowest quartile baseline ALC. Prior exposure to natalizumab or concomitant steroid, opiates or carbamazepine/oxcarbamazepine use was not associated with lymphopenia. Compared to baseline levels, CD8 T cells were significantly more reduced than CD4 cells. CD8 counts were more commonly reduced with age or white ethnicity. Subjects with BMI 25-30 was associated with a higher risk of abnormal CD4 cell count reductions. In contrast, non-smokers were more likely to experience reductions in both CD4 and CD8 counts while on DMF. CONCLUSIONS:Patients with low baseline lymphocyte counts, with intermediate BMI, with white ethnicity, with advanced age, or with no tobacco use, had a significantly higher incidence of lymphopenia on DMF. Intermediate BMI or lowest quartile baseline ALC predicted low CD4 levels, while advanced age or white ethnicity predicted low CD8 levels from DMF exposure.
Authors: Ralf Gold; Ludwig Kappos; Douglas L Arnold; Amit Bar-Or; Gavin Giovannoni; Krzysztof Selmaj; Carlo Tornatore; Marianne T Sweetser; Minhua Yang; Sarah I Sheikh; Katherine T Dawson Journal: N Engl J Med Date: 2012-09-20 Impact factor: 91.245
Authors: Collin M Spencer; Elizabeth C Crabtree-Hartman; Klaus Lehmann-Horn; Bruce A C Cree; Scott S Zamvil Journal: Neurol Neuroimmunol Neuroinflamm Date: 2015-02-12
Authors: Devangi Mehta; Catherine Miller; Douglas L Arnold; Eris Bame; Amit Bar-Or; Ralf Gold; Jerome Hanna; Ludwig Kappos; Shifang Liu; André Matta; J Theodore Phillips; Derrick Robertson; Christian A von Hehn; Jordana Campbell; Karen Spach; Lili Yang; Robert J Fox Journal: Neurology Date: 2019-03-27 Impact factor: 11.800
Authors: Mitzi J Williams; Lilyana Amezcua; Annette Okai; Darin T Okuda; Stanley Cohan; Ray Su; Becky Parks; Jason P Mendoza; James B Lewin; Cynthia C Jones Journal: Neurol Ther Date: 2020-05-29
Authors: Steffen Pfeuffer; Leoni Rolfes; Jana Hackert; Konstanze Kleinschnitz; Tobias Ruck; Heinz Wiendl; Luisa Klotz; Christoph Kleinschnitz; Sven G Meuth; Refik Pul Journal: Mult Scler Date: 2021-05-12 Impact factor: 6.312