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New marrow transplant method developed at Stanford may
eliminate fatal side effects
December 4-7, 2004. San Diego, California.
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The American Society of Hematology is the world's largest professional society concerned with the
management of blood disorders.
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STANFORD, Calif. - Bone marrow transplantation can cure
lymphomas and leukemia, but in about half of the cases
transplanted immune cells wind up attacking the patient's body,
as well as the cancer.
In response to this problem, researchers at the Stanford
University School of Medicine have developed a technique that
can virtually eliminate this life-threatening complication,
known as graft-versus-host disease, without compromising the
transplanted cells' effectiveness against cancer.
The therapy entails adjusting the patient's level of a
specific type of immune cell, the regulatory T cells, before the
transplant is done. The method was first developed in mice by
Samuel Strober, MD, professor of medicine (immunology and
rheumatology), who has been studying these types of cells for
more than 25 years. Robert Lowsky, MD, assistant professor of
medicine (bone marrow transplantation), has adapted this
strategy for humans along with Strober, and will present the
results of tests Dec. 6 at the annual American Society of
Hematology meeting in San Diego.
In two clinical trials funded by the National Institutes of
Health, Lowsky, Strober and other colleagues found that only one
of the 37 patients who received the treatment developed
graft-versus-host disease. "You would have expected something in
the order of 30 to 60 percent incidence of severe
graft-versus-host disease in these patients, according to
conventional methods," said Strober.
Studies of the new method found there was no increase in the
rate of infections in the treated patients. The studies also
found that the majority of patients who were in partial
remission went into complete remission, and those who were in
complete remission didn't relapse.
"It looks like there is a potent anti-tumor effect from our
method despite the incidence of graft-versus-host disease being
dramatically lowered," said Lowsky.
Also at the conference, Strober will conduct a session in
which he reviews the checkered history of regulatory T cells.
For years immunologists were polarized into groups who believed
in the cells, once known as suppressor T cells, and those who
doubted their existence. But with the development of more
advanced techniques for distinguishing between the different
types of immune system cells, the existence of the regulatory T
cells has been confirmed. The latest research suggests that the
regulatory T cells act as the immune system's peacekeepers,
signaling to other T cells when to hold off from attacking an
intruder.
"The news going into this meeting is that the field of
regulatory T cells has not only come out of the clouded period
that it was in, but is now being accepted and adapted into
clinical trials as a conceptual framework for achieving certain
desirable outcomes, for example in the area of bone marrow
transplantation," said Strober.
Always a proponent of the existence of regulatory T cells,
Strober worked out over the years a strategy using irradiation
and antibodies to increase the relative amount of regulatory T
cells in the immune tissues of host mice from about 1 percent of
the total T cells to more than 90 percent. By increasing the
relative amount of these cells, he found that he could retain
the desired effect of killing cancerous cells following bone
marrow transplantation, but eliminate the attack on host
tissues. "It allows you to throw out the one effect but not the
other," he said.
Lowsky said he and Strober have now taken Strober's animal
model and translated it to the clinical setting for people.
Although they have not yet gathered conclusive evidence that
this cellular process worked the same in humans as it did in
mice-that would require doing direct examinations of cells from
patients' spleens or lymph nodes-Lowsky said their evaluations
of the blood and marrow samples suggest that is the case.
Now that the method is proving to be a viable therapy for
humans, the team will be testing it with other cancer centers.
Others involved in the clinical trial are Robert Negrin, MD,
professor of medicine; Yinping Liu, MD, a staff research
associate and Judith Shizuru, MD, PhD, associate professor of
medicine, all in the bone marrow transplantation division, and
Tsuyoshi Takahashi, MD, a research fellow in Strober's lab.
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in this educational activity.
Copyright © 2004 The Doctors Lounge.
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