October 20, 2020

The Niche

Knoepfler lab stem cell blog

Stem cells for scleroderma, new NEJM article reports promise

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 Clinicaltrials.gov 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.

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