Highlights
- •Lymphocyte counts decrease during first year of dimethyl fumarate treatment.
- •Older age and lower lymphocyte counts increase the risk of lymphopenia.
- •Precipitous drop in lymphocyte counts at three months of treatment associates with lymphopenia.
- •Lymphopenic patients experience a specific decrease in NKT cells.
Abstract
Background
Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF)
as it increases the risk of progressive multifocal leukoencephalopathy.
Objective
To identify factors associated with lymphopenia in DMF-treated patients and explore
changes in blood lymphocyte subsets associated with DMF-induced lymphopenia.
Methods
Prospective longitudinal study including 106 patients initiating DMF treatment followed
for a median time of 24.67 months. Blood lymphocyte subsets were studied in 64 patients
by flow cytometry at baseline and 6 months after.
Results
Mean absolute lymphocyte counts (ALCs) decreased by 29% during the first year of DMF-treatment.
Patients developing lymphopenia showed a faster decline within the three first months.
A reduction of ALCs higher than 38% at this time was associated to subsequent development
of grade 2–3 lymphopenia (OR = 5.93, 95% CI: 1.9–18.6, p = 0.002). All patients showed a significant decrease in different T and B lymphocyte
subsets upon DMF therapy. In addition, lymphopenic patients experienced a selective
decrease in natural killer T (NKT) cell percentages (p = 0.01), and a high drop in NKT total counts (p < 0.0001).
Conclusions
Patients who experience a drop in ALCs by >38% at three months of DMF-treatment are
about 6-times more likely to develop significant lymphopenia. This decrease is clearly
associated with a considerable loss of NKT cells.
Keywords
Abbreviations:
DMF (dimethyl-fumarate), ALC (absolute lymmphocyte count)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 09, 2019
Accepted:
January 7,
2019
Received in revised form:
December 16,
2018
Received:
March 28,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
