allogeneic haematopoietic stem cell transplantation ( hsct ) , or  allografting ' , is an established treatment for haematological malignancies and genetic defects , but not autoimmune diseases ( ads ) . the risk of graft - versus - host disease ( gvhd ) and the difficulties in finding a suitable donor have hampered clinical studies on allografting in ad . yet there is a good scientific rationale for allografting in ad as it theoretically is the only treatment of ad with curative potential . its main aim is to replace a patient 's dysfunctional immune system with an allograft from a healthy donor so as to restore normal immune regulation . this is in contrast with autologous hsct , in which a patient 's own stem cells are re - infused after intensive immunosuppressive therapy . in patients with a haematological condition and concomitant ad such as rheumatoid arthritis ( ra ) or systemic lupus erythematosus ( sle ) , extensive studies in different animal models of ad have confirmed the superiority of allografting in eliminating reactivity against autoantigens and inducing sustained clinical responses . the term  graft - versus - autoimmunity ' ( gva ) effect has been coined , in analogy to the  graft - versus - leukaemia ' effect observed in allotransplanted leukaemia patients , to describe the reactivity of donor t and natural killer cells against a patient 's autoreactive lymphocytes . whether gva can occur in the absence of ( sub)clinical gvhd is a matter of debate but is an important issue as it would not make sense to exchange one ad for another . feasibility and safety of allografting have improved significantly since allogeneic bone marrow transplantation was first introduced in the clinic in the 1950s . this can be explained by the use of less intensive regimens and a switch from whole bone marrow transplants to t cell - depleted peripheral blood stem cell grafts . nowadays , so - called non - myeloablative preparative regimens that leave stem cells intact , permitting rapid reconstitution of innate immune cells and thus reducing the risk of infection , are routinely employed . the use of t cell - depleted allografts for haemato - oncological indications has reduced the risk of gvhd but at the expense of a higher risk of relapse . while undesirable , such an outcome is probably preferred over serious complications from gvhd in the case of ad . despite its theoretical appeal , allografting is still used only incidentally to treat ad , and most cases have involved patients with multiple sclerosis , ra , sle , vasculitis or systemic sclerosis ( ssc ) . both long - term remissions and relapses have been observed [ 1,7 - 9 ] . remarkably , in two patients with severe ssc , non - myeloablative conditioning resulted in 10 - 15% donor chimerism yet was sufficient to achieve complete sustained remission for more than 3 years after hsct . this suggested that full ablation of the host immune system is not a precondition to induce effective immune regulation . similar observations were made in a patient with severe refractory ra treated with non - myeloablative conditioning and hla - matched cd34-selected hsct . this patient was in remission with 55% donor t cells and 70% donor myeloid cells in blood . systematic studies in experimental animal ad have confirmed that low levels ( > 1% ) of allogeneic haematopoietic chimerism are sufficient to treat ad effectively . in a recent review of the ebmt ( european group for blood and marrow transplantation ) database , the outcome reports of 35 patients who had haematological or non - haematological ad and who collectively had received a total of 38 allogeneic transplantations were analysed . the group included two patients with behet disease , two with vasculitis , two with sle , one with dermatomyositis , and four with ra . an impressive 55% of patients reportedly had a complete response and 23% had at least a partial response , with a median duration of response of 12.3 months after hsct . this came at the expense of a treatment - related mortality at 2 years of 22.1% , however . although based on a retrospective analysis of partly incomplete data , the induction of complete remission by allografting underscores the potential clinical effectiveness . a recent proof - of - principle study in mice showed that it is possible to achieve donor stem cell engraftment in bone marrow via antibody - based clearance of haematopoietic stem cell niches . if applicable in humans , this would bypass the need for preparative regimens based on chemotherapy and reduce toxicity . ( a ) kaplan - meier plot of survival for all patients with autoimmune disease ( n = 35 ) treated with allogeneic haematopoietic stem cell transplantation . ( b ) cumulative incidence of death owing to disease progression versus transplant - related mortality . allogeneic hsct may be considered for poor - prognosis patients who have failed conventional treatment including biologicals ( ra or juvenile idiopathic arthritis ) or autologous hsct ( ssc or sle ) , which is now being examined in prospective clinical trials . nevertheless , the clinical evidence in favour of allografting is sparse and the risks are considerable . in our opinion , patients with end - stage disease or serious co - morbidities should not be transplanted . the risks of hsct in general ( both autologous and allogeneic ) may be particularly high in patients who have been heavily pre - treated with different immunosuppressive drugs , including biologicals , or who suffer from severe organ damage ( or both ) . patient selection is therefore critical and patients should be offered hsct only if they have treatment - resistant life - threatening disease yet a reasonable lifespan to allow logistical preparations for hsct to be made . patients should also have acceptable organ function to withstand unintended consequences of intensive immunosuppressive treatment and be willing to accept the risks of allografting . in terms of donor selection , sibling or matched unrelated donor transplants there is no consensus ( yet ) about the optimal transplant regimen or even the source of the graft . whether the benefits of allografting outweigh the risks can be investigated only through a prospective collaborative trial with standardised treatment regimens , uniform eligibility criteria and outcome measures , but whether such a trial is feasible remains to be seen . in the interim , it would probably be best to harmonise treatment protocols and outcome measures and collect outcome data from a comparator group of patients who are considered eligible but who do not have a suitable donor .
haematopoietic stem cell transplantation ( hsct ) has evolved from an experimental concept to an effective treatment option for severe autoimmune diseases and has a unique ability to restore immune regulation . 
 it is a complex multistep procedure involving the administration of high doses of immunosuppressive medication and transplantation of stem cells . 
 most hsct procedures in autoimmune disease have involved autologous stem cells . in the case of allogeneic transplantation , 
 stem cells are derived from peripheral blood or bone marrow of a healthy hla - matched donor . 
 allogeneic hsct has curative potential based on studies in experimental models of autoimmune disease , case reports , and a registry analysis but carries significant risks of rejection and graft - versus - host disease . 
 unless these risks become manageable , allogeneic hsct should be offered only if all alternative treatment options have failed , if a patient has a suitable donor , and if a patient still has a chance to benefit significantly from the procedure .