T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients

Abstract

Summary:Multiple sclerosis (MS) is a disease of the central nervous system characterized by immune-mediated destruction of myelin. In patients with progressive deterioration, we have intensified immunosuppression to the point of myeloablation. Subsequently, a new hematopoietic and immune system is generated by infusion of CD34-positive hematopoietic stem cells (HSC). Three patients with clinical MS and a decline of their Kurtzke extended disability status scale (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with hematopoietic stem cell (HSC) transplantation using a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg), methylprednisolone (4 g) and total body irradiation (1200 cGy). Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells. The average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of all immunosuppressive medications, functional improvements have occurred in all three patients. We conclude that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating multiple sclerosis. Stem cell transplantation has resulted in modest neurologic improvements for the first time since onset of progressive disease although no significant changes in EDSS or NRS scales are evident at this time.

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

“…13,[18][19][20] Since the first HSCT reported by Fassas et al, 21 in 1997, more than 300 HSCTs have been performed in MS patients worldwide. [22][23][24] The EBMT (European Group for Blood and Marrow Transplantation) has published the largest samples. Initially, the EBMT Group undertook a retrospective study, in which 74% of 85 patients remained stable (free of disease progression) for up to 3 years after HSCT.…”

Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease

“…Only a small number of patients undergoing HSCT for an autoimmune disease have been reported [43][44][45][46][47][48][49][50][51][52][53][54] (Table 1). All were transplanted using autologous hematopoietic stem cells.…”

Hematopoietic stem cell transplantation for multiple sclerosis: finding equipoise

“…For these reasons, phase I toxicity studies of intense immune suppression requiring HSC support were initiated in America beginning in 1996. 7 …”

“…5,6 In America, the first HSCT for MS was performed in 1996. 7 The toxicity from phase I trials will be reviewed as well as data on efficacy from the Northwestern/Milwaukee and Prague trial. Results from these studies indicate that: (1) HSCT protocols can be carried out with sufficient safety to warrant use in MS, which carries little risk of mortality but significant risk of disability provided that protocol design emphasizes safety, and (2) patients likely to respond to HSCT are likely to be found in earlier phases of disease (ie relapsing remitting MS) where active inflammatory events are more frequent and less irreversible neurological impairment has already occurred.…”