Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis

Brain. 2007 May;130(Pt 5):1254-62. doi: 10.1093/brain/awl370. Epub 2007 Feb 9.

Abstract

The present study analyses autopsy material from five multiple sclerosis patients who received autologous stem cell transplantation. A total of 53 white matter lesions were investigated using routine and immunohistochemical stainings to characterize the demyelinating activity, inflammatory infiltrates, acutely damaged axons and macrophages/microglial cells. We found evidence for ongoing active demyelination in all of the five patients. The inflammatory infiltrate within the lesions showed only very few T cells and CD8+ cytotoxic T cells dominated the T cell population. B cells and plasma cells were completely absent from the lesions. High numbers of acutely damaged axons were found in active lesion areas. Tissue injury was associated with activated macrophages/microglial cells. The present results indicate that ongoing demyelination and axonal degeneration exist despite pronounced immunosuppression. Our data parallel results from some of the clinical phase I/II studies showing continued clinical disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Axons / pathology
  • Brain / immunology
  • Brain / pathology
  • Disease Progression
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppression
  • Macrophage Activation
  • Macrophages / pathology
  • Male
  • Microglia / pathology
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / surgery*
  • Myelin Sheath / pathology
  • Nerve Degeneration*
  • Paraffin Embedding
  • T-Lymphocytes / immunology
  • Transplantation, Autologous
  • Treatment Failure