Long-Term Outcomes of Stem Cell Transplantation for Multiple Sclerosis: A Comprehensive Patient Guide

Table of Contents

• Introduction: Why This Research Matters
• Study Methods: How the Research Was Conducted
• Key Findings: Detailed Results with All Numbers
• Clinical Implications: What This Means for Patients
• Study Limitations: What the Research Couldn't Prove
• Patient Recommendations: Actionable Advice
• Source Information

Introduction: Why This Research Matters

Multiple sclerosis (MS) is a chronic neurological condition where the immune system mistakenly attacks the protective covering of nerve fibers. While many treatments can reduce disease activity in the short term, achieving long-term remission remains challenging for most patients.

Despite available therapies, more than half of patients with relapsing-onset MS continue to accumulate disability over 10 years. This is particularly concerning for those with aggressive forms of MS, characterized by severe relapses or rapid disability progression despite treatment.

Autologous hematopoietic stem cell transplantation (aHSCT) offers a different approach. This intensive treatment involves resetting the immune system using the patient's own stem cells. The goal is to eliminate self-attacking immune cells and establish lasting tolerance.

This Italian study represents one of the largest and longest investigations into whether aHSCT can provide durable, drug-free disease remission for people with aggressive multiple sclerosis.

Study Methods: How the Research Was Conducted

Researchers conducted an observational, retrospective, multicenter study involving 210 MS patients who underwent stem cell transplantation in Italy between 1997 and 2019. All patients had aggressive MS that was not responding adequately to conventional treatments.

To be included in the study, patients needed to have complete data including their age, MS type, disability score (EDSS) before treatment, details about their transplant procedure, and at least one follow-up visit after transplantation.

The treatment process involved several steps:

1. Stem cell mobilization using cyclophosphamide and filgrastim medications
2. Collection of stem cells through a procedure called leuko-apheresis
3. Freezing of the collected stem cells
4. Conditioning chemotherapy to suppress the immune system
5. Reinfusion of the patient's own stem cells

Several different conditioning regimens were used, with the most common being BEAM+ATG (74.8% of patients). This protocol includes multiple chemotherapy drugs: carmustine, cytosine-arabinoside, etoposide, melphalan, and anti-thymocyte globulin.

Patients were followed for an average of 6.2 years (with a range of up to 5 years standard deviation), making this one of the longest follow-up studies of stem cell transplantation in MS.

Key Findings: Detailed Results with All Numbers

The study included 210 patients with the following characteristics:

• 122 patients (58%) had relapsing-remitting MS (RRMS)
• 86 patients (41%) had secondary progressive MS (SPMS)
• 2 patients (1%) had primary progressive MS (PPMS)
• Median baseline disability score (EDSS) was 6 (range 1-9)
• 83.3% had detailed treatment history available

Disability Outcomes:

For all patients combined, disability worsening-free survival was 79.5% at 5 years and 65.5% at 10 years. This means nearly 8 out of 10 patients avoided significant disability progression five years after treatment.

The results varied significantly by MS type. Patients with relapsing-remitting MS showed excellent outcomes:

• 85.5% disability worsening-free survival at 5 years (95% confidence interval: 76.9%-94.1%)
• 71.3% at 10 years (95% CI: 57.8%-84.8%)
• These patients actually experienced improvement in disability scores over time
• The mean EDSS change per year was -0.09 (95% CI: -0.15 to -0.04), representing statistically significant improvement (p=0.001)

Patients with progressive forms of MS also benefited:

• 71.0% disability worsening-free survival at 5 years (95% CI: 59.4%-82.6%)
• 57.2% at 10 years (95% CI: 41.8%-72.7%)
• Disability scores stabilized with no significant worsening over time (p=0.42)

Relapse and MRI Activity:

For RRMS patients, relapse-free survival was 78.1% at 5 years and 63.5% at 10 years. The BEAM+ATG protocol showed particularly strong results with 86.4% relapse-free survival at 5 years and 77.0% at 10 years.

Treatment Protocol Differences:

The BEAM+ATG conditioning protocol demonstrated superior outcomes for preventing disease activity. Patients receiving this protocol had a 73% lower risk of NEDA-3 failure (a composite measure of no disease activity) compared to other protocols [Hazard Ratio=0.27 (0.14-0.50), p<0.001].

Safety Data:

Three patients (1.4%) died within 100 days of transplantation, which were considered treatment-related. Importantly, no deaths occurred in patients transplanted after 2007, indicating significant improvements in safety protocols over time.

Clinical Implications: What This Means for Patients

This research provides strong evidence that stem cell transplantation can induce long-term disease remission for many patients with aggressive multiple sclerosis. The treatment appears to be particularly effective for those with relapsing-remitting disease, where it not only stops progression but may actually reverse some disability.

The finding that disability scores improved in RRMS patients over 10 years is remarkable. The average reduction of 0.09 EDSS points per year might seem small, but represents meaningful functional improvement for patients when sustained over years.

The superior performance of the BEAM+ATG protocol suggests that treatment technique matters significantly. Patients considering this treatment should discuss specific protocol details with their medical team.

The safety profile has improved substantially over time, with no deaths in patients treated after 2007. This suggests that centers with extensive experience and modern protocols can perform this procedure with acceptable risk for appropriately selected patients.

Study Limitations: What the Research Couldn't Prove

This study has several important limitations that patients should understand. As an observational study rather than a randomized controlled trial, it cannot prove causation as definitively. Patients were not randomly assigned to treatment versus standard therapy.

The study included only patients with aggressive MS who had failed conventional treatments. Results might differ for those with less aggressive disease forms or those earlier in their disease course.

Treatment protocols varied across centers and over time, which might influence outcomes. The improved safety in recent years suggests that experience and protocol refinements matter significantly.

MRI data was only available for 79.5% of patients, and follow-up duration varied among participants. Longer-term data beyond 10 years will be important to fully understand the durability of response.

Patient Recommendations: Actionable Advice

Based on this research, patients with aggressive multiple sclerosis might consider the following:

1. Discuss eligibility: If you have aggressive MS not responding to conventional treatments, ask your neurologist whether you might be a candidate for stem cell transplantation
2. Seek experienced centers: The improved safety outcomes in recent years and at experienced centers highlight the importance of treatment at facilities with extensive protocol experience
3. Understand protocol differences: Ask about specific conditioning protocols, as the BEAM+ATG approach showed superior results in this study
4. Consider timing: Earlier treatment during the relapsing-remitting phase may yield better outcomes, as these patients showed both stabilization and improvement
5. Weigh risks and benefits: While the procedure carries risks, the potential for long-term drug-free remission may be worth considering for appropriate candidates

Patients should have realistic expectations. While many patients experience long-term remission, not all do. The treatment is intensive and requires careful consideration of both short-term risks and long-term potential benefits.

Source Information

Original Article Title: Long-Term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Authors: Giacomo Boffa, Luca Massacesi, Matilde Inglese, Alice Mariottini, Marco Capobianco, Moiola Lucia, Maria Pia Amato, Salvatore Cottone, Francesca Gualandi, Marco De Gobbi, Raffaella Greco, Rosanna Scimè, Jessica Frau, Giovanni Bosco Zimatore, Antonio Bertolotto, Giancarlo Comi, Antonio Uccelli, Alessio Signori, Emanuele Angelucci, Chiara Innocenti, Fabio Ciceri, Anna Maria Repice, Maria Pia Sormani, Riccardo Saccardi, Gianluigi Mancardi on behalf of the Italian BMT-MS study group

Publication: AperTO - Archivio Istituzionale Open Access dell'Università di Torino

Note: This patient-friendly article is based on peer-reviewed research originally published in neurological literature. The information has been translated for patient education but maintains all original data and findings.