Hematopoietic stem cell transplantation for treatment of autoimmune diseases

by Alexey Bersenev on October 14, 2009 · 1 comment

in clinical trials and cases

Hematopoietic stem cell transplantation (HSCT) for treatment of autoimmune diseases (AD), such as multiple sclerosis, systemic sclerosis, lupus, resistant forms of arthritis, jumped to the stage of clinical trials more than a decade ago. There was a huge demand for initiation of those clinical trials. Since that many clinical cases and small group reports were published. So what are the results? Is it worth to continue trials? Does it offer hope for many desperate patients?

The recent report summarizes all of the autologous HSCT for autoimmune diseases (AD) treatment performed in Europe during 12-years period.

This observational study (1996-2007) analysed all first AHSCT for AD reported to the European Group for Blood and Marrow Transplants (EBMT) registry. Primary end-points were overall survival (OS), progression-free survival (PFS) and the 100 days transplant related mortality (TRM).

The transplant activity in Europe by disease and years is shown this table:

MS – multiple sclerosis; SSc – systemic sclerosis; RA – rheumatoid arthritis; SLE – systemic lupus erhytematosis; JIA – juvenile idiophatic arthritis; HIC – hematological immune cytopenia
I picked one of the most important outcome characteristics, analyzed in the article – 5-years progression-free survival to illustrate efficacy of therapy.

5-years progression-free survival (PFS):

multiple sclerosis
systemic sclerosis
rheumatoid arthritis
systemic lupus erythematosis
juvenile idiophatic arthritis
hematological immune cytopenia
45% 55% 18% 44% 52% 34%

The aim of this paper was to merge the longer term follow-up of the 473 patients previously reported by the EBMT in 2003 with the cases reported to the Registry thereafter, in order to analyse the determinants of the clinical responses in 900 severe ADs patients treated by a first autologous HSCT, which is the largest number analysed worldwide so far. Our data confirm that autologous HSCT is a valid therapeutic option for patients with an AD progressing despite standard therapy.

It was no comparison of HSCT outcome with the “standard – non-transplant treatment”, but most enrolled patients were resistant to previous (standard) therapy, especially in multiple sclerosis trials.

For more details I encourage you to read a full report. It’s an open access paper.

These results sum up ten years of an EBMT-EULAR international collaborative network and form the basis for future directions in the field. They strongly support the ongoing European and North American phase III trials in severe ADs, aimed to compare autologous HSCT with standard therapies in SSc (namely, the ASTIS trial (www.astistrial.com) in Europe and the SCOT trial (www.sclerodermatrial.org) in North-America), MS (ASTIMS, www.astims.org), Crohn’s disease (ASTIC, astic@nottingham.ac.uk) and SLE (ASTIL).

It was interesting for me also to look at this EBMT report, which summarizes allogeneic HSCT for treatment of autoimmune diseases, which came up earlier this year.

Thirty-five patients receiving 38 allogeneic transplantations for various hematological and non-hematological AD were identified. Four patients had had an allogeneic HSCT for a conventional hematological indication in the past. Fifty-five per cent of the transplantation procedures led to a complete clinical response of the refractory AD and 23% to at least a partial response. The median duration of response at the last follow-up was 70.7 (15.2–130) months. Three patients relapsed at a median of 12.3 months after HSCT. Treatment-related mortality at 2 years was 22.1% (95% CI: 7.3–36.9%). Two deaths were caused by progression of AD. The probability of survival at 2 years was 70%. No single factor predicting the outcome could be identified. The retrospective nature of this study and the heterogeneous, partly incomplete data are its limitations. However, allogeneic HSCT can induce remission in patients suffering from refractory AD. These data provide the basis for carefully conducted prospective trials.

So even allogeneic transplant gave 75% of positive response. The authors conclude that results are encouraging and trials should be completed. Allogeneic transplant could be an option for some selective patients who are not suitable or previously underwent autologous HSCT.

Connotea tags: clinical trial, autoimmune, HSC transplantation

Table and quotes from the original paper used with permission of publisher. Copyright “Ferrata Storti Foundation”, Pavia, Italy.

{ 1 comment… read it below or add one }

David Peritt October 18, 2009 at 2:02 pm


Thank you so much for bringing this review to our attention. The use of HSCT for AD has been around for a long time. Anecdotal reports indicate that for many diseases the therapy is effective at resetting the immune system and decreasing clinical manifestations of the AD. However, the therapy is not widely used due to two main factors that need to be addressed before wider study and use is possible.
1. Cost – needs to come closer to cost of current AD therapeutic modalities.
2. M&M due to the HSCT – needs to be better than the AD and current modalities.


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