Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Autor: Harold L. Atkins, Daniel R. Tessier, Jason A. Berard, Gauruv Bose, Carolina A Rush, Mark S. Freedman, Hyun Woo Lee, Douglas L. Arnold, Simon Thebault, Heather MacLean, Lisa Walker, Amit Bar-Or, Ronald A. Booth, Mohammad Abdoli, Vincent Tabard-Cossa, Marjorie Bowman, Sridar Narayanan
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_treatment
Hematopoietic stem cell transplantation
Gastroenterology
0302 clinical medicine
Neurofilament Proteins
Medicine
Longitudinal Studies
Gray Matter
Research Articles
Glial fibrillary acidic protein
biology
General Neuroscience
Hematopoietic Stem Cell Transplantation
Middle Aged
Magnetic Resonance Imaging
Treatment Outcome
Toxicity
Disease Progression
Female
Neurotoxicity Syndromes
RC321-571
Research Article
medicine.drug
Adult
medicine.medical_specialty
Multiple Sclerosis
Neurosciences. Biological psychiatry. Neuropsychiatry
Young Adult
03 medical and health sciences
Clinical Trials
Phase II as Topic
Atrophy
Internal medicine
Glial Fibrillary Acidic Protein
Humans
RC346-429
Chemotherapy
business.industry
Multiple sclerosis
Neurotoxicity
medicine.disease
030104 developmental biology
biology.protein
Neurology. Diseases of the nervous system
Neurology (clinical)
business
Biomarkers
030217 neurology & neurosurgery
Busulfan
Zdroj: Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology, Vol 7, Iss 5, Pp 767-775 (2020)
ISSN: 2328-9503
Popis: Objective Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as ‘pseudoatrophy’, related to reduced inflammation. Treatment‐related neurotoxicity may be contributory. We sought objective evidence of post‐IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. Methods Sera were collected from 22 MS patients pre‐ and post‐IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single‐molecule assay. Results Pre‐IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12‐month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). Interpretation There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.
Databáze: OpenAIRE
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