Can multiple sclerosis cause leukopenia and lymphocytopenia?

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Last updated: February 27, 2025View editorial policy

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From the FDA Drug Label

5.2 Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with dimethyl fumarate. A fatal case of PML occurred in a patient who received dimethyl fumarate for 4 years while enrolled in a clinical trial. During the clinical trial, the patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5 x 109/L for 3.5 years) while taking dimethyl fumarate

The FDA drug label does not directly answer if multiple sclerosis can cause leukopenia and lymphocytopenia, but it does mention that lymphopenia has occurred in patients with MS treated with dimethyl fumarate, and that PML has occurred predominantly in patients with lymphocyte counts <0.8 x 109/L persisting for more than 6 months 1.

From the Research

Yes, multiple sclerosis (MS) can cause leukopenia (low white blood cell count) and low lymphocytes, though this is more commonly associated with the medications used to treat MS rather than the disease itself. Disease-modifying therapies like fingolimod (Gilenya), dimethyl fumarate (Tecfidera), cladribine (Mavenclad), and alemtuzumab (Lemtrada) are known to reduce lymphocyte counts as part of their mechanism of action. For example, fingolimod works by sequestering lymphocytes in lymph nodes, preventing them from circulating in the bloodstream. Regular blood monitoring is typically required for patients on these medications, with specific thresholds for dose adjustment or discontinuation. For fingolimod, absolute lymphocyte counts below 200 cells/μL may require temporary discontinuation, as seen in a study published in 2024 2. The immune dysregulation in MS itself can occasionally affect white blood cell counts, but medication effects are far more common and significant. If you have MS and develop leukopenia or lymphopenia, your neurologist should evaluate whether it's related to your treatment regimen and may adjust your medication accordingly, considering the potential benefits of switching to alternative treatments like ozanimod, as suggested by a 2024 study 2. Some studies have also identified risk factors for lymphopenia in MS patients, including lower baseline lymphocyte count and prior treatment with certain medications, such as interferon-beta 3 and natalizumab 4. Additionally, older age and lower basal lymphocyte count have been associated with lymphopenia development during dimethyl fumarate treatment, and may also be protective against disease activity 5. It is essential to weigh the benefits and risks of each treatment option and closely monitor patients for potential hematological abnormalities.

Some key points to consider:

  • Fingolimod and dimethyl fumarate can cause lymphopenia, with fingolimod being more likely to cause grade II and III lymphopenia 6
  • Switching to ozanimod may be a strategy to adjust fingolimod-related lymphopenia while maintaining clinical efficacy 2
  • Risk factors for lymphopenia include lower baseline lymphocyte count, prior treatment with interferon-beta or natalizumab, and female sex 3, 4
  • Older age and lower basal lymphocyte count may be protective against disease activity during dimethyl fumarate treatment 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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