Duke Health Referring Physicians


Long-Term Outcomes of the SCOT Trial: Benefits of Myeloablative Stem Cell Transplant in Scleroderma are Durable

Eleven years post-randomization, overall survival was significantly higher for the HSCT group than it was for the cyclophosphamide group, and other outcomes point to long-term benefits as well

Long-term follow-up of participants in the Scleroderma: Cyclophosphamide or Transplant (SCOT) trial reveals that the benefits of myeloablative hematopoietic stem cell transplantation (HSCT) in systemic sclerosis (SSc) are durable at 6 to 11 years, a new analysis finds.

Keith M. Sullivan, MD, the study’s lead author and a hematologist from Duke University in Durham, NC, presented these results at the 2018 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting, held October 19 to 24 in Chicago, IL.

“As you know only too well, scleroderma with internal organ involvement is an autoimmune disease in need of more effective treatment,” Sullivan told attendees.

The current study builds on recently published evidence from the SCOT trial that demonstrated that myeloablation followed by autologous CD 34+ HSCT significantly improved survival and function in SSc when compared with conventional treatment with monthly cyclophosphamide. 

At the beginning of the SCOT study, all 75 participants had severe scleroderma and internal organ involvement, with diffusing capacity of the lung for carbon monoxide (DLCO) or forced vital capacity (FVC) less than 70% predicted. These participants were randomized to receive either myeloablative HSCT or conventional treatment with cyclophosphamide and were followed to a 54-month endpoint; all follow-up ended at 6 years after randomization, per the protocol. 

The follow-up study was designed to determine subsequent late outcomes to HSCT or cyclophosphamide treatment. In 2017, researchers conducted scripted telephone interviews with SCOT survivors and searched public death records for all randomized study participants. The study endpoints included death and organ failure, health status and physical functioning, toxicities, disease modifying anti-rheumatic drug (DMARD) use, and quality-of-life measures.

Seventy-five percent of the HSCT group and 46% of the cyclophosphamide group completed the follow-up study. Of the original 75 participants, 18 individuals from the cyclophosphamide group were confirmed to have died since study inception versus 7 individuals from the HSCT group. Of note, 4 of the deaths in the cyclophosphamide group were newly identified in the follow-up study, whereas no new deaths were identified from the HSCT arm. Overall survival in the per-protocol (treated) HSCT study population at the 11-year post-randomization mark was 88%, with no deaths after the sixth year; in the cyclophosphamide group, 53% of individuals survived 11 years (P = .01). “Essentially, there is a 35-point difference,” Sullivan told attendees.

Other outcomes also point to long-term benefits of HSCT in SSc:

  • Organ failure developed in 2 participants from the HSCT group compared with 6 individuals from the cyclophosphamide group (P = .06)
  • At follow-up, only 8% of participants treated with HSCT were taking DMARDs compared with 39% of the cyclophosphamide group (P = .01), demonstrating continued drug-free control of scleroderma in the majority of individuals who received HSCT
  • Eastern Cooperative Oncology Group (ECOG) scores, which measure performance status, were significantly better in the HSCT group: more than 90% of those from the HSCT group had a normal (0/1) ECOG score compared with 61% of those from the cyclophosphamide group (P = .05)
  • Body weight was significantly higher in the HSCT group than in the cyclophosphamide group (P = .006)
  • More than one-half (56%) of transplant recipients were employed either full- or part-time versus just one-third of those from the cyclophosphamide group (P = .14)

Of note, none of the patients in either group subsequently developed cancer or myeloproliferative disorders after treatment.

“Long-term follow-up after randomization shows the benefit of myeloablative autologous transplant in severe SSc. The benefits are durable,” Sullivan concluded.

Source: Sullivan KM, Pinckney A, Goldmuntz E, et al. Myeloablative autologous hematopoietic stem cell transplantation for severe scleroderma: long-term outcomes 6-11 years after entry on a randomized study comparing transplantation and cyclophosphamide. Presented at: 2018 ACR/ARHP Annual Meeting; October 19-24; Chicago, IL. Abstract 1820.