Tracking the Aftermath of AHSCT in Aggressive MS: What Blood Biomarkers Tell Us

Multiple Sclerosis (MS), particularly in its aggressive form, demands urgent and effective interventions. One of the most potent therapies available for highly active MS is autologous hematopoietic stem cell transplant (AHSCT), a rigorous procedure involving high-dose chemotherapy to "reset" the immune system. While AHSCT has shown impressive results in halting disease activity, monitoring its impact—especially on the central nervous system (CNS)—has been more challenging. A recent study presented at the American Academy of Neurology Annual Meeting (Poster S37.004) by Simon Thebault and colleagues from the University of Ottawa delves into this by exploring serum biomarkers—measurable proteins in the blood that reflect CNS injury or activity. Their focus: Neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and Tau, using the ultra-sensitive SiMoA (Single Molecule Array) platform.

Why These Biomarkers?
NfL: A structural protein in neurons, elevated in blood/CSF when axons are damaged—commonly during relapses or active lesion formation in MS. GFAP: A marker of astrocyte injury or reactivity—important for understanding the role of glial cells in inflammation and healing. Tau: Linked to microtubule stability in neurons, often seen in neurodegenerative diseases but less well understood in MS. Together, these markers offer a composite picture of neuronal and glial damage as well as potential reparative responses. Study Design in a Nutshell
Subjects: 23 MS patients undergoing AHSCT and 30 non-inflammatory neurological controls.

Sampling Timeline: Blood samples were collected before AHSCT, and at 3, 6, 9, and 12 months post-treatment.

Technology Used: SiMoA assays—capable of detecting extremely low concentrations of proteins in serum.

Key Findings
1. Pre-treatment: Elevated NfL and GFAP Before transplant, both NfL and GFAP levels were significantly higher in MS patients than in controls, signaling ongoing CNS damage. Importantly, Tau was not elevated, suggesting less acute axonal degeneration involving tauopathies.

NfL also correlated with disease activity, including:

Clinical relapses within 6 months MRI findings (T2 lesion load and gadolinium enhancement)

2. 3-Month Post-AHSCT: Biomarker Spike Interestingly, rather than a smooth decline, GFAP and Tau temporarily spiked at 3 months post-transplant.

This coincided with MRI 'pseudoatrophy'—a phenomenon where rapid brain volume loss reflects resolution of inflammation and edema, rather than true atrophy.

Likely culprit: chemotherapy-induced neurotoxicity. Despite the absence of new lesions, CNS tissues appear transiently vulnerable post-AHSCT.

3. 6–12 Months: Gradual Normalization By 6 months:

NfL and Tau levels dropped to those seen in controls.

GFAP declined more slowly, remaining slightly elevated even at 12 months.

This sustained GFAP elevation could reflect ongoing astrocytic activity, potentially related to repair or remyelination processes, as inflammation subsides and the CNS enters a recovery phase.

Interpretation: What Does This Mean Clinically?
NfL is the standout biomarker—correlating well with active disease and treatment response.

The transient spike in Tau and GFAP post-treatment reminds us that not all biomarker elevations signal relapse—some reflect treatment effects or healing. GFAP’s prolonged elevation suggests that astrocytes might play a larger role in post-AHSCT CNS remodeling than previously thought.

Clinical Implications & Future Directions
Blood-based biomarkers like NfL could soon serve as routine monitoring tools to track MS activity and treatment response, reducing the reliance on frequent MRIs.

Understanding GFAP dynamics may help identify repair-promoting environments in the CNS—potentially offering targets for remyelination therapies.

Longer-term studies are needed to see whether residual GFAP elevation is predictive of long-term outcomes or repair success.

Conclusion
This study exemplifies how modern biomarker science, coupled with cutting-edge assays like SiMoA, can provide a window into the biological aftermath of aggressive MS treatment. As we move toward more personalized and precise MS care, serum NfL, GFAP, and Tau may help guide timing, assess efficacy, and even predict CNS recovery after powerful interventions like AHSCT.

References:
Thebault, S., Tessier, D., Bowman, M., et al. (2019). Serum Neurofilament, GFAP and Tau in Patients with Aggressive Multiple Sclerosis Before and After Haematopoietic Stem Cell Transplant (S37.004). Neurology, 92(15 Supplement). https://doi.org/10.1212/WNL.92.15_supplement.S37.004