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Haematopoietic stem cell transplantation for autoimmune diseases

Key Points

  • Haematopoietic stem cell transplantation (HSCT) requires a careful selection of patients according to autoimmune disease, and a consideration of therapeutic alternatives, risks and benefits, and the expertise of the transplantation team

  • The need for graft manipulation before HSCT is uncertain

  • Individualized conditioning regimens might provide increased long-term remission rates, and stem cell rescue could minimize the duration of neutropenia and improve the containment of viruses

  • HSCT resets the immune system by renewing the CD4+ T cell compartment, especially within the Treg cell population, and by restoring T cell receptor diversity and function

  • In patients with systemic sclerosis, HSCT results in increased mortality within the first year but a considerable long-term, event-free survival benefit afterwards


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.

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Figure 1: Haematopoietic stem cell transplantation in patients with severe autoimmune disease.
Figure 2: Renewal of the CD4+ T cell compartment after autologous haematopoietic stem cell transplantation.


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J.F.S. and E.M.D. researched data for article. F.V.W., J.B., J.K., J.V.L. and N.M.W. reviewed and edited the manuscript before submission. J.F.S., E.M.D., J.B. and J.K. wrote the manuscript. All authors contributed substantially to discussion of content.

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Correspondence to Joost F. Swart.

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J.K. is the co-founder and chief scientific officer of Gadeta. The remaining authors declare no competing interests.

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Swart, J., Delemarre, E., van Wijk, F. et al. Haematopoietic stem cell transplantation for autoimmune diseases. Nat Rev Rheumatol 13, 244–256 (2017).

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