Survival for Severe Scleroderma Significantly Improved with Stem Cell Transplantation

Although various treatments have been noted for their efficacy in controlling some scleroderma symptoms, rheumatologists continue to face challenges in managing outcomes for patients with severe forms of the disease. The may change as the results of a new study indicate that patients with severe scleroderma who were treated with hematopoietic stem cell transplantation (HSCT) showed significant improvement in long-term outcomes such as survival and functional status. The study was presented at the 2018 ACR/ARHP Annual Meeting, October 19-24, 2018, in Chicago, Illinois.

“Severe scleroderma with internal organ involvement (systemic sclerosis) is viewed by many rheumatologists as the most devastating of the autoimmune diseases,” study lead author, Keith M. Sullivan, MD, James P. Wyngaarden professor of Medicine at Duke University School of Medicine said in a statement. “With case mortality rates showing little change over the past 40 years, there is an urgent, unmet need to reduce its morbidity and mortality.”

Among the highlights observed in the “Scleroderma: Cyclophophamide or Transplantation” (SCOT) trial were clinical benefits of up to 11 years and superiority to cyclophosphamide (CYC) in terms of better survival and functional status in patients treated with HSCT.

A total of 75 patients with severe scleroderma were randomized into 2 groups between 2006 and 2011. Thirty-six patients received myeloablative CD34+ selected autologous HSCT and 39 patients received 12 monthly infusions of CYC. Patients were then followed to 72 months.

The investigators searched public health records to identify study participants who had died and interviewed surviving patients through scripted telephone records to assess current health status, physical functioning, toxicities, DMARD use, and quality of life. Current HAQ disability index and SF-36 health surveys were compared with last assessments.

At the time of study presentation, 7 patients treated with HSCT and 18 treated with CYC had died. Compared with 4 new deaths among those treated with CYC, no deaths were identified in the follow-up study among those treated with HSCT.

“At 11 years after randomization, Kaplan Meier estimates of overall survival were 80% vs 52% and 88% vs 53% (HSCT vs CYC; P = .03 and 0.01, respectively),” study authors wrote.

Physical functioning and weight gain improved following transplantation among 25 HSCT and 18 CYC follow-up participants. Organ failure developed in 2 HSCT (cardiac ablation and pacer) and 6 CYC recipients (3 heart failure, 2 oxygen use and lung transplant). A total of 61% of patients who were treated with CYC and 92% of patients who received HSCT remained free of immunosuppression with DMARDs.

The trial demonstrates the possibility drug-free control of scleroderma after hematopoietic stem cell transplantation.

“To show that the scleroderma has improved after transplant and results are durable for a decade off immunosuppressive drugs is a truly exciting development and a new approach to definitive treatment of autoimmune disease,” added Dr. Sullivan. “With this clear demonstration of effectiveness and durability, our current research focus is to understand why it works.”