Haematopoietic stem cell transplantation for autoimmune diseases

Autologous haematopoietic stem cell transplantation (HSCT) is the only treatment that is able to induce long-term, drug-free and symptom-free remission in several refractory autoimmune rheumatic diseases. Over 3,000 HSCT procedures for rheumatic and nonrheumatic severe autoimmune diseases have been performed worldwide. Specific conditioning regimens are currently used to eradicate the autoreactive immunological memory of patients. Although in vivo immune cell depletion with antithymocyte globulin or anti-CD52 is the norm for many regimens, ex vivo selection of CD34(+) stem cells from the graft is controversial. Following the extensive immune depletion associated with serotherapy and chemotherapy, HSCT effectively resets the immune system by renewing the CD4(+) T cell compartment, especially the regulatory T cell population. The risk of transplant-related mortality (TRM) within the first 100 days should be weighed against the risk of disease-related mortality, and the careful selection and screening of patients before transplantation is essential. Systemic sclerosis is the first autoimmune disease for which HSCT has been shown, in a randomized, controlled trial, to be associated with increased TRM in the first year but a significant long-term, event-free survival benefit afterwards. In this Review, we discuss the immunological mechanisms of HSCT in various autoimmune diseases and current HSCT regimens. After carefully taking into consideration the risks and benefits of HSCT and alternative therapies, we also discuss the efficacy, complications and proposed indications of this procedure.