A nationwide team of researchers report
on interim results from a small, five-year study of transplantation of the
individuals’ own hematopoietic (blood cell-producing) stem cells combined with
high-dose immunotherapy in 24 people with relapsing-remitting MS. This
procedure aims at “rebooting” the immune system to prevent MS immune attacks
against the brain and spinal cord. At three years, 78.4% of participants
experienced no new disease activity. When this trial has completed its
five-year duration, it will be an important addition to research needed to
determine whether this approach to stem cell transplantation is safe and
effective in people with MS. Richard A. Nash, MD (Colorado Blood Center
Institute) and colleagues report in JAMA Neurology (Published online December 29, 2014). This study
was sponsored by the National Institute of Allergy and Infectious Diseases of
the National Institutes of Health.
Background: One type of procedure that has been
explored for many years in MS is called “autologous hematopoietic (blood
cell-producing) stem cell transplantation” – or HSCT. This procedure has been
used in attempts to “reboot” the immune system, which launches attacks on the
brain and spinal cord in people with MS.
In HSCT, these stem cells (derived from
a person’s own bone marrow or blood) are stored, and the rest of the
individual’s immune cells are depleted usually by chemotherapy. Then the stored
stem cells are reintroduced back to the individual’s bloodstream. The new stem
cells migrate to the bone marrow and over time produce new cells. Eventually
they repopulate the body with immune cells. The goal of this currently
experimental procedure is that the new immune cells will no longer attack
myelin or other brain tissue, providing the person, what is hoped to be, a
completely new immune system.
The Study: Investigators enrolled 25 people who
had experienced an MS relapse involving loss of neurologic function while
taking disease-modifying therapies during the previous 18 months. Participants
received HSCT along with high-dose immunosuppressive therapy (a regimen of
treatments that profoundly suppress the immune system), and followed for five
years. The primary endpoint of this study is whether participants experience
“event-free survival,” meaning that they did not die or have an increase in
disease activity. Disease activity is defined as any one of the following
outcomes occurring: confirmed loss of neurologic function, clinical relapse, or
new lesions observed on MRI scans. The current publication presents a planned
analysis after three years of follow up.
Results: One individual experienced a pulmonary
embolism induced by heparin (administered as part of stem cell collection), and
withdrew from the study. Event-free survival at three years was 78.4%, down
from 95.8% after one year. Treatment failed in five individuals. Scores on
clinical scales measuring disease activity and quality of life, including the
EDSS, improved significantly at three years after HSCT. Immune system analysis
showed prolonged depletion of the immune cells that drive the immune attack,
indicating that the immune system was indeed “rebooted.”
Two deaths occurred, one from
complications due to MS progression and another due to asthma. One person
experienced an MS attack, an individual who had not complied with a prednisone
regimen designed to reduce this risk during collection of stem cells. There
were 130 adverse events that were severe or life-threatening, mostly cytopenias
(blood cell reductions) and infections.
Comment: Rigorous clinical trials of stem cell
therapies are crucial to determining their safety and effectiveness in people
with MS. “We look forward to seeing the completed results of this important
study,” says Bruce Bebo, PhD, Executive Vice President of Research at the
National MS Society. “There are significant risks involved in hematopoietic
stem cell transplantation, and it’s important to ensure that this will be a
safe solution for people with MS, with significant clinical benefit.”
With the urgent need for more effective
treatments for MS, particularly for those with more progressive forms of the
disease, the National MS Society believes that the potential of all types of
cell therapies must be explored. The Society is currently supporting 15
research projects exploring various types of stem cells, including cells
derived from bone marrow, fat and skin, and has supported 70 stem cell studies
over the past 10 years.
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