PARIS – Autologous stem-cell transplantation has emerged as an effective and feasible treatment for selected patients with severe systemic sclerosis who inadequately respond to conventional treatments, said two U.S. experts.
In addition, convincing evidence documenting the overall beneficial effect of autologous stem-cell transplantation will soon appear in a published report from the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, Dr. Dinesh Khanna said in a talk at the annual European Congress of Rheumatology.
In his talk, Dr. Khanna gave a short preview of the ASTIS results that he said would appear in a medical journal in the next few weeks. Those results show that among 79 scleroderma patients randomized to treatment with autologous stem-cell transplant, 8 (10%) died from treatment-related causes, compared with none in the control arm of patients who received conventional treatment with cyclophosphamide. But during follow-up, a total of 16 of the 79 (20%) stem-cell transplant patients died, compared with 24 of the 77 (31%) control patients, results that showed an overall mortality benefit from stem-cell transplantation.
The transplanted patients also showed "large improvements" in their skin score and "substantial improvements" in their forced vital capacity and in their activity as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI), noted Dr. Khanna, director of the scleroderma program at the University of Michigan in Ann Arbor.
"Before and after treatment, patients look completely different. Some patients [treated with stem-cell transplants] you can’t tell that they had scleroderma. But you need to select the right patients," he cautioned. "There is high mortality early, but if you select patients correctly the benefits will outweigh the risks. This is what we now offer to patients" who don’t respond to conventional treatments and are suitable for transplantation, Dr. Khanna said.
Researchers had previously reported these ASTIS results during the EULAR 2012 meeting.
Stem-cell treatment is appropriate for "the 10%-15% of patients with scleroderma who are the worst," commented Dr. Daniel Furst, a professor in rheumatology at the University of California, Los Angeles. "The next step is to move this treatment from the worst patients to those who are less severe. In some centers in Europe, stem-cell transplantation is becoming widely used, even for patients with only skin symptoms," Dr. Furst said in an interview.
A major attraction of stem-cell transplantation is that over time it produces regression of fibrosis and collagen deposits and healing of prior organ damage. But the treatment also carries the risk of causing substantial immunosuppression while the immune system repopulates, leaving patients vulnerable to infections and other complications.
The upcoming publication of the ASTIS findings should further cement the role of stem-cell transplantation in scleroderma management, but "I’m more of a skeptic. I would like to see it reproduced" in a second trial, Dr. Furst said. Specifically, he means the North American–based Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial now in progress. A positive result in SCOT is still needed to convince many insurers to cover the cost of stem-cell transplantation, Dr. Furst said. For example, when enrolling patients into SCOT, insurers were willing to reimburse the treatment of about a quarter of the patients who otherwise qualified for enrollment, he said.
Dr. Khanna has received research grants from 14 different drug companies. Dr. Furst has been a consultant to or speaker for 11 different drug companies, and has received research grants from 10 different companies.