Hematopoietic stem cell transplantation in systemic sclerosis: Yes!! BUT. . .

Abstract

Systemic sclerosis is a chronic multisystem, autoimmune disease with high mortality, and to date, has no effective approved therapy. For patients with the most severe forms of systemic sclerosis, autologous hematopoietic stem cell therapy has been proven to be effective, as demonstrated by three randomized controlled clinical trials and at least two registry studies. In the controlled studies, autologous hematopoietic stem cell therapy was shown to improve mortality, skin involvement, quality-of-life, and function compared with patients treated with intravenous cyclophosphamide. There is significant transplant-related mortality associated with autologous hematopoietic stem cell therapy, as well as infectious and noninfectious serious adverse events, including cardiac and renal compromise. Although the results of autologous hematopoietic stem cell therapy clinical trials to date are highly encouraging, a number of important unanswered questions remain. These include the following: What is the optimal transplant regimen; can the spectrum of systemic sclerosis patients who respond to autologous hematopoietic stem cell therapy be expanded; how can disease relapse following autologous hematopoietic stem cell therapy be predicted and managed; can treatment-related toxicity and mortality be mitigated; can response or toxicity be predicted; and finally, is there a place for allogeneic stem cell transplants in systemic sclerosis? Systemic sclerosis is an autoimmune disease with multiple immunological, vascular, and fibrotic abnormalities. Immunosuppressive therapy is frequently used, but to date its efficacy has been generally modest. Stem cell transplantation is the most potent immunosuppressive therapy currently available, and as discussed below, may have an important role in the management of systemic sclerosis.