Stem cells for scleroderma, new NEJM article reports promise

stem cells scleroderma all cause mortality
Data from on trial NCT00114530

The idea of using stem cells for scleroderma seems a bit more promising today.

A new NIH-funded study reported in the New England Journal of Medicine (NEJM) gives some hope for the use of a combination of a specific type of myeloablation and a transplant of hematopoietic stem cells (HSC). This approach yields improved long-term outcomes for patients with a severe form of scleroderma called systemic sclerosis. While survival rates for systemic sclerosis have improved it remains a very challenging condition with a significant mortality rate.

stem cells scleroderma all cause mortality
Reduction in all-cause mortality with HSCT compared to control in systemic sclerosis patients. Data from on trial NCT00114530

The new NEJM article was entitled, “Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.”

The idea behind this kind of investigational therapy is to remove as much of the autoimmune cells as possible and then replace immune function with a subsequent transplant of the patient’s own HSC’s that were harvested earlier. The hope is that this HSC transplant (HSCT) yields mature immune cells that are not auto-reactive. Encouragingly, in the new study, patients who got HSCT therapy did substantially better and fewer died than in the control group (see all-cause mortality data screenshot above.) Here are the main conclusions of the study:

“Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation.”

This kind of approach including immune system ablation is highly risky. Patients in the study in both the treatment arm and in the control (receiving cyclophosphamide alone) experienced numerous negative health events and there were some deaths. However, again systemic sclerosis is a serious, sometimes fatal illness so transformative, risky approaches are justified in my view if conducted appropriately and within the context of an IND clinical study.

You can read more about this particular study in an NIH press release. Also, the trial page has additional information. The PR notes shorter term higher risks with this new experimental therapy in patients, but apparent longer term benefits:

“Our findings indicate that undergoing stem cell transplantation for severe scleroderma poses more short-term risks but offers greater long-term gains than cyclophosphamide treatment,” said Keith M. Sullivan, M.D., of Duke University, Durham, North Carolina, who served as a principal investigator of the SCOT study. “While treatment decisions should always be made on an individual basis, we hope that our work will help define a new standard of care for this severe, life-threatening autoimmune disease.”

From the trial page you can also see a screenshot describing the HSCT treatment and control groups above.

Overall, this new study provides some real hope for using stem cells for scleroderma and avoids the hype seen sometimes in other cases of stem cells for autoimmune diseases such as scleroderma and multiple sclerosis. Here’s a recent, relevant guest post by Hamideh Emrani on another stem cell autoimmune disease trial, in that case for multiple sclerosis, with stem cells that shows some promise.


  1. I really have a question: I have an autoimmune condition known as CREST Syndrome, one of the features of which is scleroderma in a limited way. Does anyone know if there are stem-cell treatments for this disease or trials?

  2. Of note, this is the third randomized control trial for ASCT in scleroderma, all of which have shown benefit for transplantation. The control arm in all of the trials has been pulsed cyclophosphamide given monthly with somewhat variable duration of treatment and doses; cyclophosphamide was chosen as it is one of the few treatments with some modest benefit to lung function (the other one is mycophenolate mofetil). The other two trials were the ASTIS (European multi-center) and the ASSIST (Northwestern – Richard Burt) trial. I doubt there will be another major multi-center randomized trial in the near future given the difficulty in accrual, insurance barriers, etc. and I do not know of one in the offing. As such, going forward I imagine that payors, transplant centers, rheumatologists, and most importantly patients will ultimately need to make decisions about ASCT on the basis of the available data. The SCOT data are the most powerful yet in my mind.

    The short-term risks with this trial (SCOT) are mild — no early death as compared to the approximately 10% 1-year death seen in ASTIS. This may have to do with the different conditioning regimen as SCOT uniquely utilized total body irradiation and cyclophosphamide at 120 mg/kg to ablate the immune system instead of a higher dose of cyclophosphamide 200 mg/kg. Anecdotally, having treated patients on both a TBI-based and a high-dose chemotherapy regimen, the former seems to be easier but that is just personal experience/anecdote; the data are supportive of this, however. Two patients did develop myelodysplastic syndrome on the SCOT protocol which is a very serious blood disorder requiring a transplant using someone else’s stem cells, and exposure to cytotoxic chemotherapy and radiation is a well-established risk factor for this.

    The safety issues are very important, and a lot of effort has gone into ensuring patient selection is appropriate for transplant. The key is to try to select patients who are at high risk for morbidity and mortality from their underlying condition, yet have adequate organ function to proceed to transplant safely. The bulk of the transplant-related deaths have been cardiac or pulmonary in nature, and experience is very important to screen these patients carefully as a lot of the cardiopulmonary dysfunction seen may not be symptomatic (in fact, if it is symptomatic they are probably not a transplant candidate).

    I am biased as a transplant physician, but I strongly believe in ASCT for scleroderma provided that patient selection is rigorous, the transplant center has experience, and the informed consent is properly obtained. At this point, the strength of the data cannot be ignored. Of note, the European League against Rheumatism (EULAR) has listed autologous transplant as a category A recommendation for patients with rapidly progressive SSc at high risk for organ failure in their 2016 recommendations, and this was before the SCOT trial was published.

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