SCOT Study: A Potential Breakthrough;
Additional Detail About Costs and Centers That Are Actively
Enrolling
DURHAM, N.C. – In an attempt to control scleroderma,
physicians at Duke University Medical Center are leading
a national study to test whether stem cell transplants
can reconstruct defective immune systems. If successful,
the therapy would represent the first therapy ever to
treat and potentially reverse the disease itself, not
just alleviate its symptoms, said the Duke researchers.
What causes the disease is unclear, but scientists
believe a combination of genetic susceptibility and
exposure to infections or environmental toxins may trigger
its onset. Abnormal immune regulation perpetuates the
self destruction of tissue.
"Current therapies treat the disease symptoms
but they don't alter the course of the disease,"
said Keith Sullivan, M.D., a Duke oncologist in the
division of cellular therapy and the study's lead investigator.
"We are hoping that transplantation will actually
lessen or eradicate the defective immune response that
initiates and perpetuates the disease."
The Duke-led study will increase the dose and duration
of cyclophosphamide and compare this regimen against
stem cell transplants, using purified stem cells derived
from a patient's own blood.
The study—Scleroderma Cyclophosphamide or Transplantion
(SCOT)—is being funded by a $20 million grant
from the National Institute of Allergy and Infectious
Diseases (NIAID). Led by the Duke Rheumatology Division
and Adult Bone Marrow Transplant Program, the study
will enroll 226 patients at 36 institutions nationwide.
"Our hope is to apply the benefits of stem cell
transplantation to a chronic disease that can be severely
disabling to some patients and fatal for others,"
said Sullivan. "If the therapy is successful, we
could potentially extend its application to other severe
autoimmune diseases."
Autoimmune diseases are caused by defects in the immune
system that prompt its fighter T-cells to attack various
parts of the body that are mistakenly perceived as foreign.
Transplants using stem cells from bone marrow or blood
are considered a viable treatment for scleroderma because
they replace the blood-forming and immune systems that
give rise to these self -destructive abnormalities.
Stem cell transplants are traditionally used to cure
aggressive and recurrent cancers or inborn errors of
the immune system. But physicians had anecdotally observed
that patients with autoimmune disorders improved after
receiving transplants for other diseases. In 1997, a
pilot study of 35 patients with severe scleroderma confirmed
these anecdotal reports. The study was initiated by
Sullivan and Dr. Dan Furst of UCLA and was led by investigators
at the Fred Hutchinson Cancer Research Center in Seattle.
The SCOT study will compare the effects of stem cell
transplantation versus 12 monthly doses of high-dose
cyclophosphamide. The seven-year, randomized clinical
trial will evaluate differences in the death rates and
significant organ damage between the two treatment groups.
Researchers at 36 collaborating university sites will
conduct the trial while analyzing the molecular basis
of the disease and how treatments impact immune and
cellular function, gene expression, and vascular abnormalities.
"One of the primary questions we want to answer
is whether we can chronically suppress the immune system
for one year and subdue the disease, or whether we need
to completely repopulate the immune system with purified
stem cells," said Joseph Shanahan, M.D., a Duke
rheumatologist and co-investigator of the study.
Patients undergoing transplants will receive their
own, purified blood stem cells through a process called
an "autologous" transplant. Patients are first
given drugs that stimulate the release of stem cells
into their bloodstream. The stem cells are then extracted
from the blood, separated to remove lymphocytes, and
stored for future use. Only the primordial stem cells—those
which have not yet begun to commit to be a specific
cell type—will be extracted.
The patient's immune system is then destroyed using
high doses of chemotherapy and radiation: the goal is
to eradicate the immune cells responsible for attacking
the body. Following the immune destruction, the stored
blood stem cells are re-infused into the patient and
begin to repopulate the blood-forming and immune system.
Using the patient's own stem cells reduces the potential
for complications that often arise when non-self donor
blood or marrow are used.
Immune cell function will be measured pre- and post-transplant
to determine the effects of the transplant upon the
patient's immune system.
The Duke clinical team is collaborating with basic
scientists at Duke to study how the disease and its
treatments impact the immune system; blood vessel function,
size and flow; gene expression; and cellular signaling.
Other information associated with this study:
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