Neuroinflammation and Demyelination in Multiple Sclerosis After Allogeneic Hematopoietic Stem Cell Transplantation

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.