When patients with systemic sclerosis (SSc) undergo stem cell transplantation, gene activity related to immune function normalizes for up to 4.5 years after transplant.
this is, Phase 2/3 SCOT study (NCT00114530)We compared the potential benefits of stem cell transplantation with those of high-dose Cytoxan (cyclophosphamide) in severe SSc.
“Normalization of SSc [molecular] Signature…Equivalent to clinical benefit [stem cell transplant] “At this point, our findings support these disease-associated pathways as therapeutic targets,” the researchers wrote.Myeloablative surgery followed by hematopoietic stem cell transplantation results in long-term normalization of the molecular signature of systemic sclerosis“teeth, arthritis Rheumatology.
SSc, or scleroderma, is an autoimmune disease that causes scar tissue (fibrosis) to build up in the skin and sometimes in organs such as the lungs, heart, and kidneys.
Transplantation of hematopoietic stem cells (HSCs), the precursors to all types of blood cells, has been studied as a way to reset the immune system in people with SSc.
Stem cell transplant vs. Cytoxan
In SCOT, 75 adults aged 18 to 69 with severe SSc and widespread skin and visceral damage were randomized to receive either autologous stem cell transplantation or monthly Cytoxan infusions for a year. Autologous transplantation involves harvesting healthy bone marrow stem cells from the patient and a conditioning regimen to clear out any remaining stem cells before surgically reintroducing the harvested stem cells.
Data from SCOT have previously shown that stem cell transplants significantly improved patient survival compared with Cytoxan: 11 years later, the estimated survival rate for patients who received transplants was 80 percent, compared with 52 percent for those who received Cytoxan.
Before treatment, or at baseline, patients had higher activity of interferon- and neutrophil-related genes and lower activity of cytotoxic/natural killer (NK)-related genes compared to healthy people. Interferons are proteins that form part of the body's natural defences, neutrophils are immune cells involved in scar formation and release specific molecules to control the immune response, and NK cells detect and eliminate infected and cancer cells.
After 26 months, a little over two years, the changes in gene activity in the transplant recipients had normalized.
Two time points were reported here, one after 38 months, i.e. more than three years later. 19 Data are presented at 54 months (4.5 years) for 16 patients who underwent transplantation and 11 patients who were treated with Cytoxan, and data are presented at 54 months (4.5 years) for 16 patients who underwent transplantation and 11 patients who were treated with Cytoxan.
Transplant patients had decreased interferon gene activity and increased NK-related gene activity at both time points compared with baseline, “indicating normalization of the baseline SSc gene expression signature over time,” the researchers wrote. No such effect was seen with Cytoxan.
After 38 months, the transplant group had greater activity of genes associated with B cells, the immune cells that produce antibodies, and reduced expression of genes associated with myeloid cells, the white blood cells, and inflammation, compared with the healthy participants.
After 54 months, there was no difference in gene activity between the stem cell transplant group and the healthy people, suggesting that the immune system had been fully 'reconstituted.' Those treated with Cytoxan had stable gene activity and continued to have the SSc gene expression signature.
“We show [stem cell transplant] “Immune dysregulation in SSc can be normalized in the long term. These findings are consistent with the long-term clinical benefit observed with this treatment,” the researchers wrote, adding that the data contribute to the evidence that hematopoietic stem cell transplantation may be an effective disease-modifying option for severe SSc.
