Researchers at the University of Nebraska Medical Center are studying
one of the newest approaches to bone marrow transplantation they hope will
revolutionize certain cancer transplants. They are testing the safety and
effectiveness of the so-called mini-transplant in adults with leukemia
or lymphoma.
The mini-transplant, which is rapidly being accepted and studied at
transplant centers around the country, is performed as an outpatient therapy
with significantly less toxicity than with a traditional allogeneic bone
marrow transplant. Allogeneic transplants are transplants that use bone
marrow from related and unrelated donors to create a new, cancer-free immune
system in the patient.
UNMCs approach to the mini-transplant will involve using a familiar
cancer drug pentostatin — with a new twist, said Steven Pavletic, M.D.,
UNMC oncologist and associate professor of internal medicine. Dr. Pavletic
and Greg Bociek, M.D., UNMC oncologist and assistant professor of internal
medicine, are principal investigators of the study.
Pentostatin is a very old leukemia drug with a new area of application.
The drug plays an important role in suppressing the patients immune cells
during the transplant process. Theres a lot of interest in pentostatin
nationwide.
Pentostatin will be used in combination with doses of radiation six
times smaller than a traditional transplant, as well as a very gentle form
of chemotherapy, Dr. Pavletic said. Because of its mildness, mini-transplants
are expected to reduce the risk and side effects of graft-versus-host disease
a potentially fatal side effect of allogeneic transplants.
Our protocol is designed to be very non-aggressive, Dr. Pavletic said.
UNMC researchers are looking for 40 patients to enroll in the study.
Half of the patients will receive allogeneic bone marrow transplant therapy
from related donors such as relatives, and the other half will receive
bone marrow from unrelated donors through the National Bone Marrow Registry.
Those eligible for the study include patients who are responding to
standard treatments, but whose disease is at a high risk of coming back,
patients older than 60, those who cant tolerate high doses of radiation
and chemotherapy transplant, and those whose cancer returned after an autologous
stem cell transplant.
We use this therapy with patients who otherwise have very little hope.
Instead of no chance for survival, we hope we can achieve a 30 to 50 percent
cure rate. We want to find something for these patients, Dr. Pavletic
said.
The transplantation process is a delicate balance of trying to suppress
the patients immune system while trying to prevent the patients body
from rejecting the donor bone marrow cells and contracting graft versus
host disease.
The theory behind traditional allogeneic bone marrow transplantation
is to give patients high doses of radiation and chemotherapy, wipe out
the bone marrow, wipe out the disease in the bone marrow, and wipe out
the immune system to create space to infuse the donors bone marrow cells
into the patient, Dr. Pavletic said.
The theory then is that the donors bone marrow will engraft or become
part of the patient, Dr. Pavletic said. Then you have no leukemia and
you are cured. With time, what we learned, is that its not as simple as
this.
Researchers think the success of the mini-transplant lies in whats
called graft versus leukemia effect. Dr. Pavletic said he and his colleagues
have learned that donor cells are probably the most critical part of therapy.
The idea for this study was borne here in our center from our expertise
— based on our experience in transplantation and on new developments and
knowledge, Dr. Pavletic said.
The UNMC/NHS transplant program is recognized internationally for its
expertise in the diagnosis and treatment of leukemia and lymphoma, and
is one of the busiest bone marrow and stem cell transplant centers in the
world. James Armitage, M.D., started the program in 1982 with the UNMC
Lymphoma Study Group.
I think this is where transplants are going, he said. There is a
lot to be learned but the initial promise is so clear. I think the approach
of doing high-dose radiation and chemotherapy is going to be eliminated
with time probably three to five years from now. We want all this horrible
toxicity associated with allogeneic transplantation eliminated.
The mini-transplant is rapidly being accepted by transplant physicians.
I truly think its going to revolutionize the allogeneic transplantation
field. Our expectations are high, and I think the patients expectations
should be high too.
Dr. Pavletic said there are many new anti-cancer drug discoveries steadily
making cancer therapy easier and more efficient for patients. For progress
to continue, Dr. Pavletic said patients are needed to enroll in clinical
studies. Only 3 percent of patients typically enroll in clinical trials.
Clinical trials are the only way we can quickly obtain the information
we need on new drugs and treatments, he said.
One example of rapid approval by the U.S. Food and Drug Administration
took place May 10 when it granted Novartis Pharmaceuticals Corp. approval
for Gleevec, an oral therapy for the treatment of patients with chronic
myeloid leukemia in the accelerated or chronic phase after failure of interferon-alpha
therapy. Dr. Pavletic was principal investigator of the UNMC portion of
this national study.
The approval of Gleevec in two years was the most rapid FDA approval
ever, Dr. Pavletic said. This is one of the reasons why it is important
for patients to participate in clinical trials.
If we didnt have patients, we wouldnt have any of this information
yet. Some people have reservations about participating in clinical trials
like Im going to be a guinea pig, and so on. Its natural to have these
reservations. But all these trials are therapeutic. The bottom line is
we are doctors. We dont offer a trial if we think there is something better.
Drs. Pavletic and Bociek work in collaboration with a team of health
providers, including James Foran, M.D., a new UNMC acute leukemia specialist.
He said it has been known for a very long time that patients who are
involved in clinical trials tend to do better than patients who are not.
He said they get more attention, more care and have access to new drugs.
For more information about the study, call Karen Taylor at (402)
559-6729.