Bone Marrow Transplantation Study Update: Participants Treated in Study to Stop MS Progression
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Medical Update Memo
Revised February 18, 2005
(Originally Issued, Sept. 12, 2000)
Summary
The Multiple Sclerosis Scientific Research Foundation is funding
a multi-centre project
to determine definitively whether transplanting bone marrow
stem cells in people with
MS can stop the disease. Led by Dr. Mark Freedman (MS neurologist)
and Dr. Harold
Atkins (bone marrow transplant physician), both at the University
of Ottawa, the study
involves 32 people with rapidly progressing multiple sclerosis
who are likely to become
severely disabled. Twenty-four of the participants will receive
bone marrow transplantation
while eight other people with the same kind of MS but who do
not wish to have the
procedure will be the control group. Recruitment began in October
2000. The MS
Scientific Research Foundation is related to the Multiple Sclerosis
Society of Canada,
and receives most of its funding from the MS Society. This
project is funded for $4 million
over six years.
Details
As of January 2005, 17 people with MS are
enrolled in the study. One person is in the
control arm and has been followed for 34 months. Eleven people
have received transplants
to date and their follow up periods range from three to 39
months.
Generally, the transplants have been well
tolerated with mild or moderate side effects.
At this point, there have been no documented MS relapses following
the transplant procedure.
There has been one death related to chemotherapy induced liver
toxicity.
The
study was temporarily closed to recruitment from April 2003 to
March 2004 to allow the safety committee to review
the protocol. Modifications to the study protocol have been
introduced to reduce the risk of liver toxicity.
While the transplantation procedure has
been done on people with MS in the United States
and several sites in Europe, this is the first time that the
science behind the process is being
scrutinized in such detail and with the involvement of a control
group. The study also targets
younger patients, earlier in their disease course, who may
still have reversible disabilities,
and it uses a different protocol.
Bone marrow transplantation is used frequently
to treat leukemia. In a very small number
of people who have both MS and leukemia, it has been noted
that their MS improved following
the bone marrow stem cells transplant. This project should
allow investigators to
determine if bone marrow transplantation is an effective treatment
in a group of closely
matched people with MS, supporting the theories that the immune
system is key to the disease.
Equally important, should the procedure not fully stop the
disease process, the researchers may be able to detect what triggers MS early on
and discover how MS begins.
They are being monitored closely for any signs of disease activity
in the participants at all
stages of the procedure from enrolment to the end of study
three years following their
transplantation. Monitoring includes: complex immune system
tests and the tracking of certain
immune-related genetic changes in the hope of unveiling particular
genes that might
contribute to genetic susceptibility.
The study is headed by Dr. Mark Freedman
and Dr. Harold Atkins of The Ottawa Hospital
and the University of Ottawa. Co-investigators include Dr.
Jack Antel, Dr. Yves Lapierre,
Dr. Amit Bar-Or and Dr. Douglas Arnold, Montreal Neurological
Institute and McGill
University; Dr. Pierre Laneuville, Royal Victoria Hospital
and McGill University; Dr.
Pierre Duquette, Notre-Dame Hospital and the University of
Montreal; Dr. Rafick Sekaly,
University of Montreal; Dr. Hans Messner, Princess Margaret
Hospital and the University
of Toronto; Dr. Paul O'Connor, St. Michael's Hospital and the
University of Toronto; Dr.
Isabelle Bence-Bruckler and Dr. Lothar Huebsch, both at The
Ottawa Hospital.
A total of 24 people who have rapidly progressive
MS will undergo bone marrow transplantation.
A total of eight people with the same type of MS who decide
not to participate
in the study are serving as the control group.
Inclusion criteria
Participants will be invited to join the
study on the basis of the following criteria:
- Between 18 and 50 years old
Diagnosis of MS made by a neurology expert
- History of multiple early relapses within the first two
years of disease
- Having reached Expanded Disability Status Scale (EDSS)
of 3 or more within two
years of diagnosis (moderate disability in one functional
system; fully ambulatory)
- Having an EDSS score between 3 and 6 (intermittent or
unilateral constant assistance
required to walk 100m with or without resting)
- EDSS Cerebellar Functional subscore of 3 or more or
EDSS Pyramidal Functional
subscore of 3 or more (indicating at least partial
paralysis of one side of the body
[hemiparesis] or partial paralysis of the lower
limbs [paraparesis] or moderate tremor
of the arms, leg or trunk)
- MRI scan of the brain showing typical features of
MS.
The study is coordinated through the combined
efforts of The Ottawa Hospital Blood and
Marrow Transplant Program and the MS Research Clinic at The
Ottawa Hospital. The
study also involves the MS Clinic at St. Michael's Hospital,
Toronto, and the Bone Marrow
Transplant Unit at the Princess Margaret Hospital, Toronto,
as well as the MS Clinics at Notre-Dame Hospital and the Montreal Neurological Institute
and the Bone Marrow
Transplant Unit at the Royal Victoria Hospital, Montreal. Assessments
for admission to the
study will be carried out at the four clinics. Recruitment
began in October 2000.
Participants must be able to travel to and
stay in one of the treatment centre areas (Ottawa or
Montreal) for periods of time during the treatment procedure
and be able to return periodically
for monitoring. Yearly trips to Montreal for specialized MRI
scanning will also be required
for non-Montreal residents. The study coordinators will assist
with these arrangements.
Bone Marrow Transplantation Procedure
The researchers are using what is known
as autologous stem cell transplantation. They "
harvest" a portion of each person's own stem cells which
will then be used to create a
"
new" immune system once they are transplanted back into
the person. Powerful
chemotherapy drugs are used to totally eliminate from the body
the immune cells that are
attacking the protective myelin coating of the central nervous
system as well as removing
any source of their replenishment.
The following will take place, once a person
meets the study criteria and agrees to take part
in the study:
- Before receiving any treatment, participants
will have an operation to remove bone
marrow from their pelvis bones. It will be frozen and reserved
in case it is needed to
restore the immune system because of problems with regrowth
of a new immune system.
- To obtain the stem cells needed
to create the new immune system, participants will
be given Cyclophosphamide, a chemotherapy drug, and a drug
called G-CSF. It is a
medication which causes the bone marrow to grow more white
blood cells which
then enter the bloodstream. About 11 and 12 days following
the G-CSF injection, a
portion of the white blood cells containing the stem cells
will be collected from the
bloodstream via leukophereis (a procedure similar to plasma
exchange). These stem
cells will be purified to remove any trace of the old immune
cells before being
frozen and reserved.
- Three drugs will then be given (Busulphan,
Cyclophosphamide and antithymocyte
globulin) over a period of several days to destroy the participants'
existing immune
systems.
- Finally, the purified stem cells will be
thawed and given back to each individual
from whom they came in a procedure like a blood transfusion.
The entire procedure will require participants
to be hospital inpatients for several weeks.
Risks and Side Effects
The many potential risks and complications
will be explained to each participant at several
meetings before they have to decide about participating in
the study. Great caution is being
taken to ensure the health and safety of each treated participant,
but each step of this treatment
carries a risk of serious complications. These may be severe
enough in a small percentage
of patients to be fatal. A safety committee of experts in the
field of bone marrow
transplantation and MS will monitor all decisions about patient
treatment for their protection.
Participants in the study will be actively monitored for three
years including medical
examinations and periodic MRI scans.
Some of the common side effects of the treatment
include back pain, muscle aches, fatigue,
nausea, vomiting, diarrhea, dry mouth and temporary hair loss.
More severe side effects
may be serious infections and, rarely, a late life malignancy.
Information about the Study
For more information about the bone marrow
transplantation study, please contact the principal
study coordinator:
Marjorie Bowman RN, BScN
MS/BMT Research Coordinator
Phone 613 737-8104 x.7
Fax 613 737-8106
MS Research Clinic
The Ottawa Hospital
501 Smyth Rd. Rm 4104
Ottawa, Ontario
K1H 8L6
mbowman@ottawahospital.on.ca
MS Scientific Research Foundation
The MS Scientific Research Foundation is
related to the Multiple Sclerosis Society of
Canada and receives most of its funding from the MS Society.
While both organizations
fund research, the MS Society also has an extensive services
program for people with MS
and their families. For more information, contact the MS Society
at 1 800 268-7582 or
www.mssociety.ca
ASK MS Information System Code: 1.4.2.12.t
Disclaimer
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or therapy
but provides information to assist individuals in making their own decisions.
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