Stem Cell Transplant for Scleroderma

Scleroderma with internal-organ involvement (diffuse cutaneous systemic sclerosis) is a devastating autoimmune disorder. Despite advances in management, mortality driven by pulmonary involvement has not changed in 40 years. Although disease-modifying antirheumatic drugs (DMARDs) and biologics have been studied, none have shown lasting benefit, and only cyclophosphamide given for 12 months has shown short-term benefit as compared with placebo. For many patients, scleroderma is a fatal disease.

Pilot studies of autologous hematopoietic stem-cell transplantation in scleroderma showed improvement in skin sclerosis and stabilization of pulmonary function. Two randomized trials of nonmyeloablative transplantation also showed benefit; however, neither trial changed clinical practice in the United States, in part owing to concerns about durability of response and the safety of transplantation.

A study has now found new cause for optimism for Scleroderma  using an aggressive stem cell transplant regimen

The researchers, publishing in the Jan. 4 issue of the New England Journal of Medicine, found significantly improved survival among patients with a severe form of scleroderma who underwent chemotherapy, whole body radiation and a stem cell transplant. Patients also had less need for immunosuppressive drugs after transplant.

In the current study, Sullivan and colleagues developed a transplant conditioning regimen that included high-dose chemotherapy plus whole-body radiation to fully wipe out the patient’s defective immune-forming system, with the aim of improving survival and diminishing the effects of the disease. They limited radiation by shielding patients’ kidneys and lungs while repopulating the blood and immune system.

Thirty-six scleroderma patients were randomly assigned to receive transplants. The regimen was designed to destroy the patients’ defective autoreactive immune system and replace it with their own blood stem cells that had been removed and treated to eliminate self-reacting lymphocytes.

For comparison, 39 additional patients were randomized to receive 12 monthly intravenous injections of cyclophosphamide, a conventional immunosuppressive treatment for severe scleroderma.

The study was conducted over a 10-year period at 26 universities in the United States and Canada. The primary study endpoint at 54 months was a global rank composite score based on a hierarchy of scleroderma features including survival, organ function, quality of life and skin hardening.


Results showed significant benefit with transplant: 67 percent of 1,404 pairwise comparisons favored transplant vs. 33 percent favoring cyclophosphamide.

By study endpoint, fewer transplant recipients resumed use of anti-scleroderma drugs (9 percent vs. 44 percent of controls). Overall survival at 72 months was 86 percent after transplant vs. 51 percent after cyclophosphamide, a highly significant benefit.

Treatment-related mortality at the study endpoint of 54 months was 3 percent among transplant recipients while cyclophosphamide recipients had no treatment-related deaths. In the short term, transplant recipients also had more serious side effects, such as low blood counts and infections.

These advances show the value of medical research and clinical trials in finding better therapies to advance health.


Keith M. Sullivan, Ellen A. Goldmuntz, Lynette Keyes-Elstein, Peter A. McSweeney, Ashley Pinckney, Beverly Welch, Maureen D. Mayes, Richard A. Nash, Leslie J. Crofford, Barry Eggleston, Sharon Castina, Linda M. Griffith, Julia S. Goldstein,. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. New England Journal of Medicine, January 4, 2018; 378 (1): 35 DOI: 10.1056/NEJMoa170332