Autologous Hematopoietic Stem Cell Transplantation in Autoimmune Diseases

Claudio Annaloro; Francesco Onida; Giorgio Lambertenghi Deliliers

Disclosures

Expert Rev Hematol. 2009;2(6):699-715. 

In This Article

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is the most aggressive AD, frequently exhibiting a relapsing–remitting course.[131] SLE is a generalized disease and organ involvement, notably of the heart, kidney and lung, may occur early and be life threatening.[7,132] Conventional treatment relies on immunosuppressive agents and patients with refractory disease have a shortened life expectancy.

Owing to extensive tissue and organ extension, SLE seems to be the paradigm of 'central' AD, where a primary disorder of the immune system, and possibly of the HSC, plays a major pathogenetic role.[133] On the other hand, a considerable rate of disease-related mortality in refractory patients makes some degree of TRM acceptable.[134] The combination of these two considerations suggest that autologous HSCT may be a 'pathogenetic' and cost-effective treatment in SLE patients. In MS and SS, the best studied indications to autologous HSCT, the main targets are improvement/stabilization of disease in the former and improvement in skin disease with stabilization of deep organ involvement in the latter, whereas in SLE improvement in organ dysfunction has proved to be a target within the scope of the procedure.[7,135] The same goes for antiphospholipid syndrome, since most patients are able to discontinue anti-thrombotic prophylaxis after autologous HSCT.[136] In SLE, immunologic resetting by autologous HSCT bears the potential of affecting the pathogenetic clues of disease and of getting closer to some kind of cure. This view is reinforced by a recent paper showing that SLE autografting-induced CR is the result of depletion of autoreactive memory cells and of their substitution by a normalized repertoire of graft-derived younger T cells.[137] Similar benefits were also observed in B cells. These findings may be interpreted as an attempt at re-establishing self-tolerance. This wealth of evidence points to autologous HSCT in SLE as a possibly curative therapeutic strategy.

Systemicus lupus erythematosus disease activity index (SLEDAI) is a well-accepted instrument to determine disease status and response to therapy.[62] SLE has been among the first indications to autologous HSCT, since severely ill patients seemed to justify the risk of TRM;[131] this led to the publication of single case reports where autografting was able to induce unexpected response in patients with desperately advanced disease.[7,132,138–144] On the other hand, autologous HSCT in SLE has not gained the same degree of interest as in MS or SS. Therefore, both the number of small monocentric series[41,134,135,145,146] and of transplanted patients in registry surveys[131] are notably low.

The main results deriving from the available experiences concern the possibility of disease flare-up after mobilizing regimen, the preference to immunoablative conditioning regimen, the combination of both 'in vitro' and 'in vivo' lymphodepletion, generally through positive CD34 selection and ATG administration (with ATG delivered more frequently than CD34 selection performed) and the considerable (though unequally reported[146]) rate of TRM.[9,131,134,147] On the other hand, surviving patients have a considerable chance of achieving disease remission and an half to up to two thirds of remitters may experience long-term treatment-free survival.[41,57,131,135,146,147]

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