Autologous Stem Cell Transplantation for Multiple Sclerosis: Real-World Outcomes and Patient Implications

Table of Contents

• Introduction: Understanding Stem Cell Treatment for MS
• Study Methods and Patient Selection
• Patient Characteristics Before Treatment
• The AHSCT Treatment Process
• Key Findings: Efficacy Outcomes
• Safety Profile and Adverse Events
• Factors Affecting Treatment Outcomes
• What This Means for Patients
• Study Limitations
• Patient Recommendations
• Source Information

Introduction: Understanding Stem Cell Treatment for MS

Autologous hematopoietic stem cell transplantation (AHSCT) represents a promising treatment approach for multiple sclerosis that aims to reset the immune system and stop the inflammatory attack on the nervous system. This procedure involves collecting a patient's own stem cells, using chemotherapy to suppress the immune system, and then reinfusing the stem cells to rebuild a new immune system without the autoimmune activity that characterizes MS.

The research published in Neurology examines how this treatment performs in real-world clinical practice rather than strictly controlled trial settings. This distinction is important because real-world studies include a broader range of patients who more closely represent the general MS population, providing valuable insights into how the treatment works outside ideal research conditions.

Study Methods and Patient Selection

This retrospective study analyzed 120 multiple sclerosis patients treated consecutively between 2012 and 2019 at two London medical centers: King's College Hospital and Hammersmith Hospital. Researchers included all patients who had at least 6 months of follow-up data or who died at any point after treatment, ensuring comprehensive capture of outcomes.

The research team established strict eligibility criteria to identify appropriate candidates for AHSCT. Patients needed a confirmed MS diagnosis according to McDonald criteria, to be between 18-65 years old, with disease duration since diagnosis of 15 years or less, and an Expanded Disability Status Scale (EDSS) score between 0 and 6.5. Crucially, patients needed to show evidence of "inflammatory active MS" demonstrated by MRI activity within the previous 12 months.

For patients with relapsing-remitting MS (RRMS), an additional requirement was treatment failure with at least one high-efficacy disease-modifying therapy (DMT), including medications like alemtuzumab, mitoxantrone, natalizumab, or ocrelizumab. Each case underwent multidisciplinary team review involving both neurologists and transplantation hematologists to ensure appropriate patient selection.

Patient Characteristics Before Treatment

The study population represented a diverse group of MS patients with varying disease courses. Of the 120 participants, 58 (48%) had relapsing-remitting MS, 40 (33%) had secondary progressive MS, and 22 (18%) had primary progressive MS. The cohort had a nearly equal gender distribution with 58 females (48%) and 62 males (52%).

Patients had a mean age of 42.3 years and average disease duration of 8.9 years since diagnosis. The median EDSS score at baseline was 6.0, indicating moderate to significant disability where patients typically require assistance to walk. Importantly, 90% of evaluable patients showed MRI activity in the 12 months preceding treatment, confirming active inflammatory disease.

Previous treatment history revealed that patients had tried an average of 1.7 disease-modifying therapies before undergoing AHSCT. Those with RRMS had tried more treatments (average 2.3) compared to progressive forms. Seventy patients (58%) had previously tried at least one high-efficacy DMT, with 19 having received alemtuzumab and 58 having received natalizumab.

The AHSCT Treatment Process

The treatment process followed standardized protocols at both medical centers with some variations in specific procedures. The process began with stem cell mobilization using cyclophosphamide chemotherapy followed by granulocyte colony-stimulating factor (G-CSF) to stimulate stem cell production. At King's College Hospital, most patients received cyclophosphamide 4g/m² over 2 days, while Hammersmith Hospital used 2g/m² over 1 day.

Conditioning chemotherapy before stem cell infusion used cyclophosphamide (50 mg/kg for 4 days) and rabbit anti-thymocyte globulin (rATG) for in vivo lymphodepletion. The median CD34+ stem cell dose collected was 7.17 × 10⁶/kg at King's College and 7.75 × 10⁶/kg at Hammersmith. Patients remained hospitalized for a median of 22 days, with neutrophil engraftment occurring at a median of 12 days after transplantation.

Significant differences emerged between the two centers in treatment details. King's College Hospital had longer inpatient stays (median 26 days vs 20 days) and longer time to neutrophil engraftment (median 13 days vs 11 days), possibly related to their higher cyclophosphamide dose during mobilization.

Key Findings: Efficacy Outcomes

The study demonstrated impressive efficacy outcomes across multiple measures of disease activity. The annualized relapse rate dropped dramatically from 0.46 ± 0.57 in the 2 years before transplantation to 0.08 ± 0.38 in the post-treatment follow-up period, representing a statistically significant reduction (p < 0.001).

Relapse-free survival rates were excellent: 93% of all patients remained relapse-free at 2 years after AHSCT, and 87% at 4 years. Importantly, all relapses after treatment occurred only in patients with RRMS, and within that subgroup, relapse-free survival was 87% at 2 years and 77% at 4 years.

MRI outcomes showed equally impressive results. Ninety percent of participants had no new MRI lesions detected at 2 years after treatment, and 85% remained lesion-free at 4 years. The reduction in new T2 lesions was statistically significant (p < 0.0001) when comparing the 12 months before treatment to the follow-up period of up to 4 years after transplantation.

Disability outcomes showed more variation between MS subtypes. The average EDSS score change was +0.25 during the 12 months before treatment but only +0.02 in the 12 months after therapy. Patients with RRMS showed平均 improvement in EDSS scores (-0.17), while those with progressive MS showed continued deterioration (+0.24).

Longer-term disability outcomes measured by confirmed EDSS worsening showed that 75% of the whole population remained free from disability progression at 2 years, decreasing to 65% at 4 years. There was no significant difference in disability progression between RRMS and progressive MS subgroups.

Safety Profile and Adverse Events

The safety data revealed significant treatment-related risks that patients must carefully consider. Almost 90% of treated patients experienced at least one early complication after AHSCT. The most common adverse events included fever, infections, gastrointestinal symptoms, and various treatment-related complications.

Tragically, there were 3 treatment-related deaths within 100 days of transplantation, representing a 2.5% mortality rate. All three deaths occurred after fluid overload and cardiac or respiratory failure. Two patients had primary progressive MS (ages 58 and 42), and one had RRMS (age 51), all with EDSS scores of 6.5 at baseline.

Further analysis revealed that fluid overload (defined by >5% weight gain with edema requiring additional diuretics) occurred in 78 of 118 patients (66%), typically presenting about 3 days after the first dose of anti-thymocyte globulin. Center differences emerged in complication rates, with King's College Hospital showing higher rates of fever, positive cultures, neutropenia, and readmission after mobilization, possibly related to their higher cyclophosphamide dose.

Factors Affecting Treatment Outcomes

The researchers conducted detailed analyses to identify factors that might predict treatment success or failure. They found that Epstein-Barr virus (EBV) reactivation and monoclonal paraproteinemia (abnormal proteins in the blood) were associated with worse outcomes for disability progression.

Statistical analysis identified high paraprotein levels (>5 g/L) as the only significant variable associated with confirmed EDSS score progression over 4 years, with an odds ratio of 1.07 (95% confidence interval 1.03-1.10, p < 0.001). Interestingly, paraprotein levels did not predict relapses or new MRI lesions, suggesting a specific relationship with disability progression rather than inflammatory activity.

Viral reactivations were common after treatment, with cytomegalovirus detected in 26 cases requiring preventive treatment. Epstein-Barr virus reactivation occurred in 63 patients (53%), typically around 41 days after transplantation, with most cases resolving spontaneously without specific treatment.

What This Means for Patients

This real-world study provides compelling evidence that autologous stem cell transplantation can effectively suppress multiple sclerosis activity for extended periods. The high rates of relapse freedom (93% at 2 years) and MRI activity suppression (90% lesion-free at 2 years) demonstrate that AHSCT can significantly alter the disease course for many patients.

The differential outcomes between MS subtypes carry important implications for treatment decisions. Patients with relapsing-remitting MS showed actual improvement in disability scores after treatment, while those with progressive forms continued to worsen, though at a potentially slower rate. This suggests that timing of intervention is crucial, with better outcomes expected when treatment occurs during the inflammatory phase of MS rather than after significant neurodegeneration has occurred.

The substantial risk profile, including a 2.5% mortality rate and high incidence of serious complications, underscores that AHSCT remains an intensive treatment requiring careful patient selection and management at experienced centers. The fluid overload complications observed in 66% of patients highlight the need for vigilant monitoring and preventive measures during treatment.

Study Limitations

This study has several important limitations that affect how we interpret the results. As a retrospective analysis rather than a randomized controlled trial, the evidence is rated Class IV, the lowest level of evidence according to neurological research standards. The lack of a control group means we cannot definitively attribute outcomes to the treatment rather than natural disease variation.

The relatively short median follow-up of 21 months (range 6-85 months) limits our understanding of long-term outcomes beyond 4 years. Additionally, the single-arm design prevents direct comparison with other treatments or with untreated patients, making it difficult to assess the relative benefits against newer high-efficacy disease-modifying therapies.

Center differences in treatment protocols and patient management introduce variability that may affect outcomes. The higher cyclophosphamide dose at one center appeared associated with longer hospital stays and different complication profiles, suggesting that protocol optimization remains an ongoing process.

Patient Recommendations

Based on this research, patients considering autologous stem cell transplantation for multiple sclerosis should:

1. Seek treatment at experienced centers with multidisciplinary teams including both neurologists and transplantation hematologists
2. Consider timing carefully - earlier intervention during the relapsing-remitting phase appears associated with better outcomes
3. Undergo thorough pre-treatment evaluation including assessment for risk factors like potential for fluid overload
4. Have realistic expectations about both the substantial benefits and the significant risks, including the 2.5% mortality rate
5. Participate in long-term follow-up to contribute to our understanding of extended outcomes beyond 4-5 years

Patients should discuss these findings with their healthcare providers to determine whether AHSCT represents an appropriate treatment option given their specific disease characteristics, previous treatment history, and personal risk tolerance.

Source Information

Original Article Title: Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series

Authors: Richard S. Nicholas, PhD; Elijah E. Rhone, MD; Alice Mariottini, MD; Eli Silber, MD; Omar Malik, MD, PhD; Victoria Singh-Curry, MD; Ben Turner, MD; Antonio Scalfari, MD, PhD; Olga Ciccarelli, MD, PhD; Maria P. Sormani, PhD; Eduardo Olavarria, MD; Varun Mehra, MD, PhD; Ian Gabriel, MD; Majid A. Kazmi, MD; and Paolo Muraro, MD, PhD on behalf of the London Group on Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Publication: Neurology 2021;97:e890-e901. doi:10.1212/WNL.0000000000012449

This patient-friendly article is based on peer-reviewed research published in Neurology, the medical journal of the American Academy of Neurology.