Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial

Study Objective

The primary objective of this study was to assess the effect of intense immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) compared to mitoxantrone (MTX) in patients with multiple sclerosis (MS). The study specifically measured disease activity through the use of MRI imaging.

Methodology and Trial Design

This multicenter, phase II, randomized trial included patients with secondary progressive or relapsing-remitting MS. Eligible participants had a documented increase in the Expanded Disability Status Scale (EDSS) within the last year despite receiving conventional therapy, and the presence of one or more gadolinium-enhancing (Gd+) areas.

Patients were randomized into two treatment arms:

• AHSCT Group: Received mobilization with cyclophosphamide and filgrastim, followed by conditioning with carmustine, cytosine-arabinoside, etoposide, melphalan, and anti-thymocyte globulin.
• MTX Group: Received 20 mg of mitoxantrone every month for a duration of 6 months.

Study Endpoints

The primary endpoint was defined as the cumulative number of new T2 lesions during the 4-year follow-up period. Secondary endpoints included the following metrics:

• Cumulative number of Gd+ lesions
• Relapse rate
• Disability progression
• Safety and tolerability assessments

Key Results

Out of 21 randomized patients, 17 provided evaluable post-baseline MRI scans. The results demonstrated that AHSCT reduced the number of new T2 lesions by 79% compared to MTX (rate ratio 0.21, p = 0.00016). Additionally, AHSCT significantly reduced Gd+ lesions and the annualized relapse rate. However, no significant difference was observed regarding the progression of disability.

Conclusion

The study concludes that intense immunosuppression followed by AHSCT is significantly superior to MTX in reducing MRI-detected disease activity in severe cases of MS. These findings strongly support the initiation of phase III studies focusing on primary clinical endpoints.