Dartmouth study identifies severe scleroderma patients most likely to benefit from stem cell transplant

by Berit Svenson |

Patients with hard-to-treat scleroderma will be happy to learn that an effective therapy for their painful autoimmune rheumatic disease may be soon in sight. A multi-center study by researchers at Dartmouth and other institutions found that a subset of patients who suffer from scleroderma are more likely to benefit from hematopoietic stem cell transplant than cyclophosphamide, the more standard drug therapy.

Scleroderma, a rare autoimmune disease that affects the skin, blood vessels, muscles and internal organs, currently has no treatments approved by the U.S. Food and Drug Administration, according to Michael Whitfield, interim chair and biomedical data science professor at the Geisel School of Medicine.

The study demonstrated that stem cell transplant is an effective therapy for patients with severe scleroderma.

“If you get this disease in its most severe form, there are not a lot of good treatments that physicians could put you on right now,” Whitfield said. “Stem cell transplant looks like a treatment that will really be helpful for some of the most severe patients with [scleroderma].”

Geisel quantitative biomedical sciences doctorate candidate Jennifer Franks, the lead author of the study, said that Dartmouth became involved in the study to look at the patients’ gene expression at a molecular level and analyze why the treatment worked for some patients but not others.

Using a machine learning classifier developed by Franks, patients were grouped into three subsets based on their gene expression. Patients who benefited from the transplant were part of the fibroproliferative group, while those classified in the normal-like subset responded similarly to both the transplant and the cyclophosphamide, suggesting that they do not benefit from stem cell transplant, according to Franks.

The study found that in the fibroproliferative subset, patients who underwent a transplant experienced significant improvement in their condition compared to fibroproliferative patients who received cyclophosphamide.

“Stem cell transplants are dangerous and invasive procedures that cost a lot of money,” Franks said. “So if patients aren’t likely to see a lot of benefit from them, it doesn’t make sense to treat them with a transplant versus a more standard therapy.”

According to Geisel research scientist Viktor Martyanov, a second author of the study, the research team has worked on creating a personalized medicine approach for scleroderma. Different patients may respond differently to the same treatment due to the heterogeneous nature of the disease, Martyanov said.

“We want to be able to predict which patients are likely to benefit from which drugs,” he said.

This study is the first time that researchers could prove that certain subsets of gene expression predict patients’ responses to therapy, according to Whitfield.

“We’ve put together this method by which we can take the patients, look at their molecular signatures, and define who is going to improve the most and who is going to probably not improve on this therapy,” Whitfield said.

Martyanov added that health care costs could eventually be reduced as a result of these findings by narrowing down effective treatment options for individual patients.

Since the study has spanned several years, researchers were able to see the long-term effects of the treatments, according to Martyanov.

Franks added that the rareness of scleroderma creates a “tight-knit community of clinicians and researchers” working to create an effective treatment for the disease.

“It’s been quite a collective effort from multiple research groups toward trying to find as many discoveries [as possible] from this very large trial,” Martyanov said. “Hopefully these discoveries can ultimately benefit the field of scleroderma in general, and most importantly, patients with scleroderma in particular.”

Correction appended (Nov. 7, 2018): This article has had its headline updated to reflect that this was not the first successful clinical trial in an autoimmune disease.