A new study led by Duke Health researchers found significantly improved
survival rates among patients who received an aggressive stem cell transplant
regimen to treat a severe form of scleroderma as compared to those who only
received the immunosuppressant
aggressive stem cell transplant regime to treat systemic sclerosis, a
severe form of scleroderma that affects the internal organs, significantly
improved survival rates among patients.
- In this study,
high-dose chemotherapy and radiation were given to patients to deplete the
bone marrow and was followed by autologous Stem Cell Transplant (with cells that were taken
out prior to the study and treated) or 12 doses of the immunosuppressant
. The findings of this research appeared in the
January 4 issue of the New England
Journal of Medicine
is an autoimmune disease that is characterized by hardening of the skin and connective tissues. Scleroderma
can be localized or systemic. The
localized form of the disease is relatively mild and usually affects only in a few parts of the skin or
muscles, and rarely spreads elsewhere. Systemic scleroderma or sclerosis is a disorder of the blood vessels
(vasculopathy), low-grade inflammation and development of excess fibrous
connective tissue in the skin and internal organs.
This form of the
disease is debilitating and potentially lethal, and treatment options
available for it are limited.
People with systemic sclerosis try to cope by
managing the symptoms. They may take antirheumatic
drugs and immunosuppressant drugs like cyclophosphamide
for this purpose,
but none of these medications have been proven to provide long-term benefits.
‘Infusing patient’s own treated blood stem cells after destroying the bone marrow improved the survival and quality of life in patients with severe scleroderma.’
"Scleroderma hardens the skin and connective
tissues and in its severe form leads to fatal organ failure, most often the
lungs" said lead author Keith Sullivan, Professor of Medicine and Cellular
Therapy at Duke University. "In these severe cases, conventional drug
therapies are not very effective long-term, so new approaches are a
use of stem cell transplant for systemic sclerosis
In two clinical trials performed earlier,
patients received non-myeloablative HSCT, where a less
intensive treatment of chemotherapy was used without any radiation; at these
doses, the bone marrow was not destroyed completely. These studies showed that
stem cell transplant used this way with reduced-intensity chemotherapy improved
survival in severe scleroderma. The drawback of this kind of treatment was that
the disease often returned and patient safety remained a concern. Hence, the
clinical practice of using conventional immunosuppressive drug treatment
continued to be the standard of care in the US.
Cyclophosphamide or Transplantation (SCOT) trial: Does myeloablative transplant
regimen offer better long-term outcomes?
SCOT trial compared the safety and potential benefits of the two treatment
regimens for systemic sclerosis, myeloablative stem cell transplant and
were 75 participants with diffuse systemic sclerosis with lung or kidney
involvement included in the study.
In the patients who received myeloablative autologous hematopoietic stem
cell transplant (HSCT)
, the doctors collected the participants'
blood-forming stem cells. Chemotherapy
and radiation were then employed
to destroy the normal and cancerous cells in the bone marrow, followed by
transplantation of the person's own blood-forming stem cells to reconstitute
the marrow and immune system.
six scleroderma patients were assigned in
the study to receive myeloablative autologous HSCT. On the other hand, thirty
nine patients were randomized to receive one year of treatment
with monthly doses of intravenous cyclophosphamide, a conventional
immunosuppressing treatment for severe scleroderma.
The results of the study were as follows:
- Participants who received a transplant
experienced significantly better outcomes overall than those who received
cyclophosphamide: 67 percent
of 1,404 pairwise comparisons favored transplant vs. 33 percent favoring
- In addition, fewer transplant recipients resumed the use of antirheumatic
drugs for progression of their scleroderma (9 percent) as compared to 44
percent of participants in the cyclophosphamide group.
- The overall
survival at 72 months was significantly better in the transplant group (86
percent after transplant vs. 51 percent after cyclophosphamide).
effects of the Treatments
in both study arms experienced known short-term risks, such as infections and
low blood cell counts. Although the overall infection rates in both the arms
were similar, transplant recipients were more prone to infections caused by
varicella zoster, the virus that causes chickenpox
- During the study, lesser patients in the
transplant arm died (7), compared to the cyclophosphamide arm (14); this
included deaths that occurred due to disease progression (2 with
transplant versus 11 with cyclophosphamide).
- Equal number of deaths (3) occurred in both arms
among those who did not complete the treatment.
the treatment-related deaths were two in number in the transplant category
and none in the cyclophosphamide category.
"Patients and their doctors should carefully
weigh the pros and cons of intensive treatment with stem cell transplant, but
this may hopefully set a new standard in this otherwise devastating autoimmune
disease," Sullivan said. "These advances show the value of medical
research and clinical trials in finding better therapies to advance
- KM Sullivan et al. Myeloablative autologous stem cell transplantation for severe scleroderma. N Engl J Med 2018; 378:35-47January 4, 2018. DOI: 10.1056/NEJMoa1703327
- Stem cell transplant for severe scleroderma improves survival, quality of life - (https://www.nih.gov/news-events/news-releases/stem-cell-transplant-severe-scleroderma-improves-survival-quality-life)