Scleroderma, an autoimmune disease in which the patient’s own immune system attacks the skin and connective tissue causing it to harden, is a progressive and often lethal condition with few treatment options. A new clinical trial by investigators at Vanderbilt University Medical Center (VUMC) and other leading medical centers found that an intensive transplant treatment using the patient’s own stem cells can improve survival and quality of life for patients with advanced scleroderma.

The 10-year study, conducted at 26 clinical research sites in the United States and Canada, was published in the New England Journal of Medicine, and Keith Sullivan, MD, at Duke Health served as lead author.

“Far too many patients die from this disease and we have been searching for improved therapies for these individuals,” said co-author Leslie Crofford, MD, Wilson Family Professor of Medicine and chief of the Division of Rheumatology and Immunology at VUMC and a member of the steering committee for the trial.

“This is a landmark clinical trial in a relatively understudied field and VUMC researchers were instrumental in the design and completion of the study.”

For the new clinical trial, dubbed SCOT (Scleroderma: Cyclophosphamide or Transplantation), investigators compared cyclophosphamide, a standard immune-suppression drug, versus a regimen known as myeloablative autologous hematopoietic stem cell transplant. The stem cell therapy includes a conditioning regimen of high-dose chemotherapy and total body radiation to destroy the patient’s flawed immune system, followed by transplantation of the person’s own stem cells to reconstitute the bone marrow and immune system.

For the SCOT trial, 36 scleroderma patients with advanced disease including lung or kidney involvement were randomly assigned to receive the transplant. For comparison, 39 patients were randomized to receive 12 monthly intravenous injections of cyclophosphamide.

“We found the new stem cell transplant regimen to be superior to the conventional treatment using only immune-suppressing drugs,” said study co-author Kristine Phillips, MD, PhD, associate professor of Medicine at VUMC. “Previous studies that did not include irradiation had suggested that stem cell transplants could be helpful, but this was the first trial using a more intensive regimen to wipe out the patient’s own immune system prior to transplant.”

At the primary study endpoint of 54 months, patients were evaluated for survival, organ function, quality of life and skin hardening. Only 9 percent of transplant patients needed to resume treatment with anti-scleroderma drugs because of disease progression versus 44 percent of cyclophosphamide patients.

At 72 months, 86 percent of transplant patients were still alive versus 51 percent of patients receiving cyclophosphamide, a significant difference.

During the study, two deaths in the transplant arm were attributed to the treatment, which is a lower transplant-related death rate than previously reported for stem cell therapy.

There were no treatment-related deaths among cyclophosphamide patients.

Participants who received transplants were much less likely to die from progression of their scleroderma than patients in the other study arm.

Only two transplant patients died from disease progression, versus 11 deaths among those who received an adequate regimen of cyclophosphamide.

In the short term, more transplant patients experienced serious side effects such as infections or low blood counts.

“The results from the SCOT trial suggest that scleroderma patients who receive this form of transplant therapy may have better long-term outcomes with more side effects in the short term,” Crofford said. “Patients and their physicians should review the benefits and risks of this transplant regimen, but it is encouraging to have this new treatment option available for patients.”