Haematopoietic stem cell transplantation for autoimmune diseases

Abstract

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.

CRISPR-Cas Genome Surgery in Ophthalmology

“…The differentiation and proliferative potential of these cells theoretically can lead to replacement of diseased tissue in patients and allow scientists to study human disease in vitro with increased precision, potentially tailored to the individual patients from which the cells were derived. 87–89 Deriving stem cells from patients offers specific advantages for testing targeted therapeutics and autologous transplantation with reduced risk of rejection. 88 Induced pluripotent stem cells (iPSCs) are stem cells that can be generated from patient tissue by reprogramming processes, and they have greatly enhanced the study of human disease.…”

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

“…45,46 While those are validated, indication for HSCT is defined individually and according to the experience of the center, as this approach is still an experimental therapy. 42,47 Normalization of raised serum interleukin-18 (IL-18) levels has recently been demonstrated posttransplant, hence serum IL-18 may potentially be a useful biomarker to assess disease activity of sJIA in this context. 48,49 Of note, a potential disadvantage of allo-HSCT following a failed autologous procedure is the possibility of adding comorbidities, especially from severe infections (eg, patient 1).…”

Cure of Insulin-Dependent Diabetes Mellitus by an Autologous Hematopoietic Stem Cell Transplantation Performed to Control Multiple Myeloma in a Patient with Chronic Renal Failure on Regular Hemodialysis

“…More than 3000 HSCT procedures for severe AIDs have been performed worldwide and the published clinical trials that included sufficient follow-up have demonstrated safety and efficacy of HSCT for AIDs [75,76]. However, the most beneficial effects of stem cell therapies in AIDs are those performed for severe refractory AIDs, particularly systemic sclerosis where a randomized clinical trial has shown significant long-term PFS benefit of HSCT [75][76][77].…”