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

Neurology. 2015 Mar 10;84(10):981-8. doi: 10.1212/WNL.0000000000001329. Epub 2015 Feb 11.

Abstract

Objective: To assess in multiple sclerosis (MS) the effect of intense immunosuppression followed by autologous hematopoietic stem cells transplantation (AHSCT) vs mitoxantrone (MTX) on disease activity measured by MRI.

Methods: We conducted a multicenter, phase II, randomized trial including patients with secondary progressive or relapsing-remitting MS, with a documented increase in the last year on the Expanded Disability Status Scale, in spite of conventional therapy, and presence of one or more gadolinium-enhancing (Gd+) areas. Patients were randomized to receive intense immunosuppression (mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine-arabinoside, etoposide, melphalan, and anti-thymocyte globulin) followed by AHSCT or MTX 20 mg every month for 6 months. The primary endpoint was the cumulative number of new T2 lesions in the 4 years following randomization. Secondary endpoints were the cumulative number of Gd+ lesions, relapse rate, and disability progression. Safety and tolerability were also assessed. Twenty-one patients were randomized and 17 had postbaseline evaluable MRI scans.

Results: AHSCT reduced by 79% the number of new T2 lesions as compared to MTX (rate ratio 0.21, p = 0.00016). It also reduced Gd+ lesions as well as the annualized relapse rate. No difference was found in the progression of disability.

Conclusion: Intense immunosuppression followed by AHSCT is significantly superior to MTX in reducing MRI activity in severe cases of MS. These results strongly support further phase III studies with primary clinical endpoints. The study was registered as EUDRACT No. 2007-000064-24.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Female
  • Gadolinium
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Image Enhancement
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Mitoxantrone / pharmacology*
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Chronic Progressive / therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Multiple Sclerosis, Relapsing-Remitting / therapy*
  • Transplantation Conditioning / methods*
  • Transplantation, Autologous
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Gadolinium
  • Mitoxantrone