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Jian-Qiang Lu, MD; Jeffrey T. Joseph, MD; Richard A. Nash, MD; Jan Storek, MD; Anne M. Stevens, MD; Luanne M. Metz, MD; Arthur W. Clark, MD; Edward S. Johnson, MD; V. Wee Yong, PhD

Arch Neurol. 2010;67(6):716-722.

Objective  To evaluate the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the brains of persons with and without multiple sclerosis (MS) by means of postmortem histopathological examination.

Design  Postmortem histopathology, case studies, and case-control studies.

Patients  Four patients with MS who died at a median of 4.5 months (range, 3-9 months) after allo-HSCT for a concomitant hematologic malignant neoplasm; 5 patients without MS who died at a median of 10.0 months (1-29 months) after allo-HSCT; and 5 control subjects without MS who did not undergo allo-HSCT.

Setting  Referral centers.

Intervention  Allogeneic hematopoietic stem cell transplantation.

Main Outcome Measures  Morphological features and immunohistochemical features, including the quantitative measures of chronic inflammatory cells.

Results  Demyelinating and inflammatory activities of MS persisted after allo-HSCT in all of the patients with MS. Active and chronic active MS lesions exhibited significantly higher numbers of CD3⁺ T cells and CD8⁺ cytotoxic T cells and significantly higher scores of CD68⁺ microglia/macrophages than did chronic inactive lesions or normal-appearing white matter. The normal-appearing brains of allo-HSCT recipients who did not have MS were found to have significantly higher numbers of CD3⁺ T cells and CD8⁺ cytotoxic T cells and higher scores of CD68⁺ microglia/macrophages compared with the controls; however, no demyelination was identified in these non-MS samples.

Conclusion  Allo-HSCT fails to halt the demyelination and inflammation of MS.

Author Affiliations: Departments of Pathology and Laboratory Medicine (Drs Lu, Joseph, and Clark), Internal Medicine (Dr Storek), and Clinical Neurosciences and Hotchkiss Brain Institute (Drs Metz and Yong), University of Calgary, Calgary, Alberta, Canada; Fred Hutchinson Cancer Research Center (Dr Nash) and Department of Pediatrics, University of Washington (Dr Stevens), Seattle; and Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada (Dr Johnson). Dr Lu is now with the Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton.

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