Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directions

Abstract

Around 700 patients have received an autologous haematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease (AD). The majority of these have been within the context of phase I/II clinical trials and following international guidelines proposed 7 years ago. In general, a positive benefit/risk ratio has led to phase III prospective randomized controlled trials in multiple sclerosis (MS), systemic sclerosis (SSc) and rheumatoid arthritis (RA) in Europe. In the US, similar trials are being planned for SSc, MS and systemic lupus erythematosus (SLE). Transplant related mortality (TRM) has fallen in all disease subgroups since the inception due to more appropriate patient selection, and so far a clear advantage of the more intense myeloablative regimens in terms of remission induction and relapse rate has not emerged. Although each AD has a different profile, over a third of patients have sustained a durable remission, often with no further need for immunosuppressive drugs. In those who relapsed, many responded to agents which pre transplant had been ineffective. The study of immune reconstitution and gene expression pre and post HSCT is being undertaken to further understand the mechanism of autoimmunity.

Figures

Fig. 1

(a,b) are T1 weighted MRI brain scans with gadolinium contrast medium of a patient with multiple sclerosis. The inflammatory lesions in 1a seen pre — stem cell transplant are absent in 1b performed one month post transplant. However, the area of demyelinization and atrophy (‘black hole’) remains. Courtesy of J Mancardi for the GITMO group and Blackwell Publishing [53].

Fig. 2

Clinical outcome in 85 patients.

Fig. 3

Clinical outcome in 57 patients followed up to 60 months post transplant.

Fig. 4

Clinical outcome in patients followed up to 55 months.

Fig. 5

Clinical outcome in patients followed up to 78 months post transplant.