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Despite
being the preferred therapy for various types
of leukemia, less than 4,000 allogeneic bone
marrow transplants take place annually in the
US, which sees more than 29,000 cases of leukemia
a year. Lack of fully matched family donors
is an important factor restricting the use of
allogeneic bone marrow transplants.
Transplantation
from matched unrelated donors (MUD) has become
a viable alternative for patients without a
suitable related (family) donor. Clinical outcomes
for such patients are dependent on a number
of variables, among them disease status, degree
of HLA match between recipient and donor, age
of patient, and prevention of complications
such as severe acute GvHD.
Matching
Donors
The
national Marrow Donor Program in Minneapolis,
Minn. averages 3,000 donor searches at any given
time, and 75 percent of these searches are for
patients with leukemia. Depending on the racial
and ethnic background, patients have up to an
80 percent chance of finding at least one potential
match.
After an unrelated
donor bone marrow transplant, severe GvHD remains
a serious risk, afflicting 40 percent (unreleated
6/6 match) to > 60 percent (unrelated 5/6
match) of patients, as compared to <20 percent
of patients who receive a transplant from an
HLA-identical sibling.
Traditional GvHD
prophylaxis with drugs is often ineffective
for MUD transplant. Existing T-cell depletion
techniques are effective in reducing GvHD, but
lead to increased risk of graft failure, leukemic
relapse, and B-cell lymphoproliferative diseases.
Chimeric's
study
Chimeric
Therapies, (www.chimeric.com),
a biotechnology company headquartered in Laguna
Niguel, Cal., has developed a proprietary technology
which claims to perform T-cell depletion of
bone marrow grafts without losing the subsets
responsible for engraftment and relapse prevention.
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The
company, with the collaboration of NMDP, has
started a pivotal phase II/III study to evaluate
the safety and efficacy of their processing
technique in patients with acute or chronic
leukemia.
IBMT's involvement
The company
invited 20 experienced unrelated donor transplant
centers to participate, which include MD Anderson
Hospital in Houston, TX; Cleveland Clinic in
Cleveland, OH and Indiana Blood and Marrow Transplantation.
This study randomizes
patients younger than 50 years of age with a
6/6 matched unrelated donor and patients younger
than 35 years of age with a 5/6 matched unrelated
donor to receive either processed or non-processed
bone marrow. Patients in both arms of the study
will receive tacrolimus (FK506; PrografDDD and
methotrexate as GvHD prophylaxis.
"The primary
objectives will be to decrease severe acute
GvHD and to enhance survival at day +100; secondary
objectives include engraftment, moderate acute
GvHD and disease-free survival at six months.
Additional, non-randomized,
studies will use this BM processing technique
for transplantation into patients who are at
even higher risk of dying from severe acute
GvHD, such as patients 35 to 50 years of age
who have a 5/6 matched unrelated donor, or patients
receiveing haplo-identical related stem cell
grafts.
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