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Newswise — CHICAGO – New research at the 2018 ACR/ARHP Annual Meeting builds on current evidence that hematopoietic stem cell transplantation can significantly improve long-term outcomes for patients with severe scleroderma when compared to use of conventional treatment with cyclophosphamide (Abstract #1820).

Scleroderma is a chronic disease that causes the skin to become thick and hard and may damage internal organs such as the heart, lungs, stomach and kidneys. The effects of scleroderma vary widely and range from minor to life-threatening, depending on how widespread the disease is and which parts of the body are affected.

Rheumatologists have been challenged in managing disease outcome although various treatments have been effective in controlling some scleroderma symptoms.  In the “Scleroderma: Cyclophophamide or Transplantation” (SCOT) trial, 75 severe scleroderma patients with internal organ involvement were randomized to receive myeloablative CD34+ selected autologous hematopoietic stem cell transplantation (HSCT) or 12 monthly infusions of cyclophosphamide (CYC)  and followed for clinical outcomes.

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

In 2017, the researchers conducted scripted telephone interviews with scleroderma participants in the SCOT trial. The follow-up study’s endpoints included time to death or organ failure. They also solicited the following health measures: current health status, physical functioning, toxicities, disease-modifying anti-rheumatic drug (DMARD) use and quality of life. They compared Health Assessment Questionnaire disability index and SF-36 health survey data to the patients’ last assessments. Public death records were also searched for all randomized study participants.

Out of 75 randomized participants in the trial, seven treated with the stem cell transplants and 18 treated with CYC have died. No deaths were identified in the follow-up study among those treated with stem cells compared to four new deaths among those treated with CYC. At the 11-year mark after randomization, Kaplan Meier actuarial estimates of overall survival were 80 percent for stem cell transplantations versus 52 percent for CYC in the intention-to-treat population.

Among 25 stem cell transplant and 18 CYC follow-up participants, physical functioning and weight gain were improved following transplantation. Organ failure developed in two transplant patients and six CYC participants. Stem cell transplant participants also reported a significantly better performance status than the CYC group. Additionally, 92 percent of stem cell transplant participants remained free of immunosuppression with DMARDs compared to 61 percent of CYC participants.

Overall, the findings show that hematopoietic stem cell transplantation’s clinical benefits are durable six to 11 years after randomization, and survival and functional status are significantly better than CYC. This trial also demonstrates continuing drug-free control of scleroderma after hematopoietic stem cell transplantation.

“This study now extends follow-up of the study to six to 11 years after randomization. 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,” said Dr. Sullivan. “With this clear demonstration of effectiveness and durability, our current research focus is to understand why it works. Fundamental discoveries include demonstration that after hematopoietic stem cell transplantation, but not after conventional cyclophosphamide treatment, the genomic signatures of scleroderma resolve, suggesting establishment of a genomic new normal after autologous stem cell transplant”.


About the ACR/ARHP Annual Meeting

The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, if offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit https://www.rheumatology.org/Annual-Meeting, or join the conversation on Twitter by following the official #ACR18 hashtag.

About the American College of Rheumatology

The American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit www.rheumatology.org.


Abstract #: 1820

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

Keith Sullivan1, Ashley Pinckney2, Ellen Goldmuntz3, Beverly Welch4, Dinesh Khanna5, Robert W. Simms6, Suzanne Kafaja7, George Georges8, Jan Storek9, Mary Ellen Csuka10, Richard E. Nash11, Daniel E. Furst12, Leslie Crofford13, Peter McSweeney11, Maureen D. Mayes14 and Lynette Keyes-Elstein2, 1Duke University Medical Center, Durham, NC, 2Rho Federal Systems, Inc., Chapel Hill, NC, 3NIAID, NIH, Bethesda, MD, 4National Institutes of Health, Bethesda, MD, 5Division of Rheumatology, Department of Internal Medicine, University of Michigan Scleroderma Program, University of Michigan, Ann Arbor, MI, 6Boston University School of Medicine, Boston, MA, 7David Geffen School of Medicine, UCLA, Los Angeles, CA, 8Fred Hutchinson Cancer Research Center, Seattle, WA, 9University of Calgary, Calgary, AB, 10Medical College of Wisconsin, Milwaukee, WI, 11Colorado Blood Cancer Institute, Denver, CO, 12University of Washington, Seattle, WA, 13Vanderbilt University Medical Center, Nashville, TN, 14University of Texas, Houston, TX

Background/Purpose: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial demonstrated that for adults with severe scleroderma (ACR 1995 criteria) and internal organ involvement, myeloablative CD34+selected autologous hematopoietic stem cell transplantation (HSCT) led to significantly improved clinical outcomes compared to 12 monthly infusions of cyclophosphamide (CYC)1. Participants were randomized between 2006 and 2011 and followed to 72 months. We report here survivor status, late effects and outcomes 6-11 years after randomization on the SCOT trial.

Methods: We conducted scripted telephone interviews with survivors and searched public death records in mid-2017. Endpoints included time to death or organ failure (see table). Current health status, physical functioning, toxicities, DMARD use and quality of life measures were solicited, and the current HAQ disability index and SF-36 health surveys compared to last assessments.  Events are listed as occurring before or after prior reporting1.                                                                                        

Results: Of 75 randomized SCOT participants, 7 HSCT and 18 CYC recipients have died. For HSCT, no new deaths were identified in the follow-up study compared to 4 new deaths for CYC (table A).  Overall survival is depicted in the intention-to-treat (figure A) and per-protocol  (received HSCT or >/= 9 doses CYC) (figure B) populations. At 11 years after randomization, Kaplan Meier estimates of overall survival were 80% vs 52% and 88% vs 53% (HSCT vs CYC; Figure A and B, p=0.03 and 0.01, respectively).

Among the 25 HSCT and 18 CYC follow-up participants, physical functioning and weight gain were improved following HSCT (table B).  Organ failure developed in 2 HSCT (cardiac ablation and pacer) and 6 CYC recipients (3 heart failure, 2 oxygen use and lung transplant). No subsequent malignant or myelodysplastic events were observed.  Performance status was significantly better after HSCT while employment rates and measures of physical and social functioning trended higher but were not statistically different. DMARDS were being taken by 2 HSCT and 7 CYC recipients, with 92% and 61% of the two respective treatment groups remaining DMARDs-free (p=0.01).

Conclusion: This follow-up analysis demonstrates that the clinical benefits of HSCT previously reported1 are durable 6-11 years after randomization. Survival and functional status were significantly better with HSCT, and continuing control of scleroderma was demonstrated by 92% of transplant survivors remaining free of DMARDs and disease.

Reference:  1Sullivan KM, et al. N Engl J Med 2018; 378:35-47.

Disclosures: K. Sullivan, None. A. Pinckney, None. E. Goldmuntz, None. B. Welch, None. D. Khanna, None. R. W. Simms, None. S. Kafaja, None. G. Georges, None. J. Storek, None. M. E. Csuka, None. R. E. Nash, None. D. E. Furst, None. L. Crofford, None. P. McSweeney, None.


Meeting Link: 2018 ACR/ARHP Annual Meeting