Successes and Failures of Stem Cell Transplantation in Autoimmune Diseases

Abstract

Over the past 15 years, more than 1500 patients have received HSCT, mostly autologous, as treatment for a severe autoimmune disease (AD). More than 1000 of these have been registered in the European Group for Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) combined database. A recent retrospective analysis of 900 patients showed that the majority had multiple sclerosis (MS; n ϭ 345) followed by systemic sclerosis (SSc; n ϭ 175), systemic lupus erythematosus (SLE; n ϭ 85), rheumatoid arthritis (RA; n ϭ 89), juvenile idiopathic arthritis (JIA; n ϭ 65), and idiopathic cytopenic purpura (ITP; n ϭ 37). An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplantation-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Approximately 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many patients, such as in those with SSc, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented beyond any predicted known effects of intense immunosuppression alone. The high TRM was in part related to conditioning intensity, comorbidity, and age, but until the results of the 3 prospective randomized trials are known, an evidence-based modification of the conditioning regimen will not be possible. 1 In recent years, multipotent mesenchymal stromal cells (MSCs) have been tested in various AD, exploiting their immune-modulating properties and apparent low acute toxicity. Despite encouraging small phase 1/2 studies, no positive data from randomized, prospective studies are as yet available in the peer-reviewed literature.

Remission of refractory Crohn's disease by high‐dose cyclophosphamide and autologous peripheral blood stem cell transplantation

“…This finding is consistent with the other published trials of autoPBSCT for the treatment of CD, 8,15 however, the number of transplanted patients and experience regarding potential long-term complications is still limited. AutoPBSCT-related mortality in patients with autoimmune diseases has been reported to range between 1% and up to 10% in patients with systemic sclerosis, 23,24 which is likely due to significant lung and heart involvement in these patients. The application of this invasive and interdisciplinary therapy should therefore be restricted to centres with longstanding experience in both, management of inflammatory bowel disease as well as PBSCT.…”

Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

“…[19][20][21][22] Hematopoietic stem cell transplantation has also shown dramatic positive outcomes in various autoimmune diseases, including SLE. 23 …”

Mesenchymal Stem Cell treatment for autoimmune diseases: a critical review

“…Undoubtedly MSC therapy must be further explored in SLE. The EULAR Stromal Cell Group is now conducting a prospective, double-blind, comparative, multicenter trial of renal lupus treated with allogeneic MSCs (Tyndall, 2011).…”