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Cellular Therapy of Autoimmune Disease

by Dr. Tyndall • November 1, 2008

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The desired immunoablative effect of HSCT, on the other hand, comes along with an increased susceptibility to infections. This is the case mostly for bacteria or fungi during aplasia (up to 14 days after induction therapy), and this is also the case during the phase of immune reconstitution that can be delayed up to several months. During the latter, the patients are at risk for opportunistic infections or reactivation of silent viruses.

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Explore This Issue
November 2008

Results of HSCT for Autoimmune Diseases

Data on the effect of HSCT on patients suffering from autoimmune diseases are obtained from retrospective case series, the EBMT/European League Against Rheumatism (EULAR) database, and from published phase I/II trials.

Up until March 2008, the EBMT/EULAR database included results from nearly 1,000 patients who received an HSCT for the indication autoimmune disease registered. Among these patients, more than 900 received an autologous HSCT and around 50 an allogeneic HSCT. Indication for autologous HSCT have been multiple sclerosis (MS) in 353 patients, SSc in 176, systemic lupus erythematosus (SLE) in 85, rheumatoid arthritis in 86, and other autoimmune diseases in fewer patients. (See Table 1, below left.) Most often, peripheral blood stem cells have been used as a stem-cell source but, in 65 cases, bone marrow was used. In more than one-third of the patients, in vitro CD34 positive selection had been performed.

The results of the phase I/II trials and registered case reports have been published.2 In essence, two publications have shown that around 50% of SLE patients achieved remission at some stage post-transplant,4,5 and, in MS and SSc, durable remission occurred in one-third. (See Figure 3, p. 22.) Transplant-related mortality was highest in the multicenter SLE series, but in general, that is now less, due to more stringent patient selection.

In SSc, it has been recently shown that HSCT is not just a once-only immunosuppression. HSCT also seems to be able to reverse fibrosis6,7 and improve micro-vascularisation.8,9

A prospective trial called the Autologous Stem Cell Transplantation International Scleroderma trial (ASTIS) is nearing completion in Europe, comparing HSCT with 12 monthly cyclophosphamide IVI pulses; in the United States, the Scleroderma Cyclophosphamide or Transplant (SCOT) trial is running. Both have similar designs with the exception of the treatment arm of SCOT, which includes limited radiotherapy.

Limited experience is available with allogeneic HSCT for autoimmune disease.10 Although offering the theoretical advantage of a “healthy” immune system, the real risk of GvHD and its attendant morbidity and mortality has limited this form of HSCT to small series and case reports.

The Future of HSCT for Autoimmune Disease

There are now significant data suggesting that a profound immunoreduction supported by autologous stem cell rescue may alter the natural history of some autoimmune disease, with most experience being in SSc. The initial treatment is hazardous, with potentially lethal complications such as cardiotoxicity or overwhelming infection.

Pages: 1 2 3 4 5 6 7 8 | Single Page

Filed Under: Departments, Medical Education Tagged With: autoimmune, research, stem cells, technology, treatmentIssue: November 2008

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