Abstract Details

Title Circulating Hematopoietic Stem Cell Numbers during Natalizumab Treatment in Patients with Multiple Sclerosis: Association with Clinical and MRI Variables

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 194

Objective

Background BACKGROUND: We previously showed clear inter-individual differences among Natalizumab-treated patients allowing us to define "Mobilizer" and "Non-mobilizer" profiles. HSC-mobilization failure correlated with poor response to treatment.

Design/Methods DESIGN/METHODS: Flow-cytometric enumeration of CD45-low/CD34+ circulating HSC in 13 prospectively followed natalizumab-treated patients: a HSC "Mobilizer" was defined based on a ?3-fold increase in circulating HSC after two months of treatment compared to baseline. Correlations between HSC number and patient demographics, EDSS score, relapse rate and MRI activity.

Results RESULTS: Circulating HSC increased significantly during natalizumab and inter-individual differences were observed among patients at baseline and during the first two months of treatment. Of 13 patients, 6 were "Non-mobilizer" and 7 were "Mobiliser"; in the latter, HSC counts increased up to 14-fold after the first infusion. We observed a trend to correlation between HSC-"Non-mobilizer" status and each of the following: longer disease duration; lower number of relapses and gadolinium-enhancing lesions during the year preceding starting natalizumab; shorter duration of previous treatments. Interim correlations in a patients' subgroup evaluated with MRI at six months on natalizumab showed that a "Mobilizer" status (found in 50%) was associated with stable T2 lesion load and absence of gadolinium enhancement, whereas a "Non-mobilizer" status was associated with increased T2 lesion number and/or presence of gadolinium enhancements.

Conclusions CONCLUSIONS: We confirm in a validation cohort that natalizumab induces widely different HSC-mobilization responses. We also show that "Non-Mobilizer" status is associated with a less inflammatory-active disease phenotype at baseline. The ongoing follow-up will allow ascertaining the potential association of HSC-mobilizer status with response to treatment, described in our original study cohort and suggested by the current analysis.

Authors/Disclosures
Miriam Mattoscio, MD, PhD, FAAN (Barking Havering and Redbridge University Hospitals Trust) PRESENTER	Dr. Mattoscio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MERCK SERONO. Dr. Mattoscio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MERCK SERONO.
Richard S. Nicholas, FRCP (Imperial College Healthcare Trust)	Dr. Nicholas has nothing to disclose.
Omar Malik, MD	No disclosure on file
Paolo Muraro	Paolo Muraro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cellerys. Paolo Muraro has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Pinsent Masons LLP. Paolo Muraro has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Taylor Wessing LLP. Paolo Muraro has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Bugge Valentin. Paolo Muraro has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Lambert Hornby LLP. The institution of Paolo Muraro has received research support from NIHR-EME. The institution of Paolo Muraro has received research support from Benaroya Research Institute.
	No disclosure on file

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