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BY MERRY
SUE BAUM
"For some
people, a stem cell transplant is an alternative where there is no
other, " says Roger K. Strair, MD, associate professor of medicine at
UMDNJ-Robert Wood Johnson Medical School (RWJMS).
One such
person was Olga Rabke. While on a trip to her native Italy, Rabke
suddenly experienced what felt like a pulled muscle in her groin. When
she returned home to Scotch Plains in March, she went to her physician.
Except for being slightly anemic, she was given a clean bill of health.
He did recommend, however, that she see an orthopedist. She did, and he
discovered she was suffering from multiple myeloma, or cancer of the
bone marrow that causes tumors to form inside the bones. An x-ray
showed that her femur looked like "Swiss cheese."
She
started her search for an oncologist. Her neighbor, Rohit Sharma, MD, a
student at RWJMS at the time, recommended Strair. She liked him
immediately. "He said a few words to me in Italian," she says, "and he
took the time to explain everything to me. I felt like I was in very
good hands." He recommended an autologous stem cell transplant for his
new patient.
According
to Strair, who is also director of stem cell transplantation at The
Cancer Institute of New Jersey, the procedure, which has been in use
for about a decade, has often proven effective in the treatment of
multiple myeloma, lymphomas, leukemias, Hodgkin's disease, aplastic
anemia, testicular cancer and some congenital immunodeficiency
diseases.
Bone
marrow transplants were at one time the ultimate treatment for these
disorders. And depending on an individual's history and the disease, it
is still the preferred therapy.The procedure begins by either taking
some of the patient's own marrow and freezing it, or finding a suitable
donor.
Next, high
doses of chemotherapy and radiation are given to the patient to destroy
the cancer-causing cells. While this is perhaps the most grueling part
of the treatment, the physician says often it is not nearly as horrific
as it's portrayed. "Some people don't get very sick," he says. "And we
have drugs that are very effective for controlling nausea."
After the
chemotherapy and radiation have been completely metabolized by the
body, the preserved or donated marrow is given to the patient via a
transfusion. If all goes well, the stem cells in the transplanted bone
marrow will give birth to a generation of tumor-free blood cells in
about 15 to 25 days.
A stem
cell transplant is, in essence, a bone marrow transplant with several
distinct differences. Andrew L. Pecora, MD, a UMDNJ-New Jersey Medical
School (NJMS) alumnus and director of the Marrow and Stem Cell
Transplant Program at Hackensack University Medical Center, explains.
"In a bone marrow transplant, the stem cells are in the marrow," he
says. "In a stem cell transplant, they are harvested from the
circulating bloodstream." Stem cells taken from the bloodstream
multiply much faster, so new cells form within only five to 15 days.
Since the white cells - the body's defense system - are produced much
faster than in a bone marrow transplant, the patient is far less likely
to contract a life-threatening infection. Hospital stays, if needed at
all, are shorter, and costs are significantly reduced. To stimulate
stem cells to move into the bloodstream, a patient is given
chemotherapy and a growth hormone for 10 to 14 days, or a growth
hormone alone for five days. He or she then goes through an almost
painless harvesting procedure known as leukophoresis. It is done on an
outpatient basis, in a special stem cell laboratory, and is much like
getting a blood transfusion. A needle is inserted into a vein and blood
is slowly removed and run through a leukophoresis machine. The stem
cells are filtered out, counted, and the remaining blood is pumped back
into the patient. The patient next gets high doses of chemotherapy
and/or radiation, the stem cells are infused again through a vein and
they "home" to the bone marrow and begin making new cells.
There are
three types of marrow and stem cell transplants: autologous, in which
the patient's own marrow or stem cells are transplanted; syngeneic, in
which marrow or stem cells from an identical twin are used; and
allogeneic, in which marrow or stem cells from another person with
similar blood and tissue types are used.
"Allogeneic
is much more complicated," Pecora says. "Patients undergo prolonged
therapy with immunosuppressant drugs to avoid rejection of the new bone
marrow. The drugs lower the white cell count making the patient very
susceptible to infections. They must take antibiotics and be monitored
very closely."
But the
upside, he says, is that the new marrow or stem cells are highly
unlikely to be contaminated with tumor cells, so the chances of
recurrence are lowered. Also, the patient now has a different immune
system that may see the tumor cells as foreign and kill them.
An
autologous transplant is much safer. "Everyone survives," he says, "but
there is always the chance that a few tumor cells got into the
harvested marrow or stem cells, and the disease will return. Syngeneic
is probably ideal: there is next to no chance of rejection and no
chance of contamination. However, most people don't have an identical
twin."
In
Rabke's case, she first received chemotherapy to mobilize the stem
cells into the bloodstream. Throughout the chemotherapy, she continued
teaching Italian, as she had for years, at area book stores and adult
high schools. "I'm very strong," she says. "Sometimes students would
come to my house if I was too tired, but I was never really sick."
After
having a chest catheter inserted as an outpatient at Robert Wood
Johnson University Hospital in New Brunswick, Rabke underwent three
sessions, about six hours each, of leukophoresis. Next came two days of
high doses of chemotherapy. She and her husband stayed in a hotel
nearby while she received the treatments. One day later, November 1,
her own stem cells were infused back into her body through the chest
catheter. "It was a big day for me," she says. "I finally made it to
the end of the road."
Rabke says
she lost her hair, which was probably the most traumatic part of the
treatment. And it took about three months for her appetite to return,
but once it did, she was her old self. "Dr. Strair said I didn't need
vitamins, I should just eat well. I'm Italian. I love to cook. So I ate
well."
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BENEFITS OF UMBILICAL CORD BLOOD
Patients
with certain blood or bone marrow diseases (such as leukemia or
congenital immunodeficiency diseases) can be cured by replacing their
diseased blood-forming cells with normal blood stem cells from healthy
donors. This procedure is called stem cell transplantation. After
chemotherapy and/or radiation to reduce or eliminate their diseased
blood cells, patients receive transfusions of the donors' blood or
marrow stem cells, which begin producing new blood cells within a few
weeks.
The immune cells transplanted among the donor cells can benefit the
patient by fighting against the patients' diseased cells. In some
cases, however, the patient's body can be attacked by the donor's
transplanted immune cells because the patient's and donor's immune
systems recognize each other as 'foreign.' Such an attack, called graft
vs. host disease or GVHD, can lead to serious disability or death, even
after the original disease has been eradicated. In order to reduce the
risk of severe GVHD, the donors' cells must be closely matched to the
patients' immune system markers (termed HLA typing). If the patient has
healthy siblings, the chance of a complete match is approximately 1 in
4 for each sibling. Cells from incompletely HLA-matched siblings are
likely to cause clinically significant GVHD. Cells from unrelated
donors, even if matched, are more likely to cause clinically
significant GVHD due to immune system mismatches that are not
identified in HLA typing. Unfortunately, it is often difficult to find
even unrelated matches for individuals of ethnic minorities (i.e.,
non-Caucasians in the United States) among the traditional bone marrow
(stem cell) registries.
It has long been recognized that blood from umbilical cords of newborn
babies contains higher numbers of stem cells than adult blood. Cord
blood is collected after delivery of the placenta, without any risk or
discomfort to mother or baby. Since the late 1980s, several hundred
stem cell transplants for both children and adults with either
malignant or non-malignant diseases have been performed using unrelated
cord blood when no matched siblings were available. In general, the
results have been better in children with non-malignant diseases;
however, many adults with malignant blood diseases have had very long
disease-free survivals.
Cord blood cells are immunologically immature and seem to better
tolerate the patients' tissues, resulting in lower frequency and
severity of GVHD than adults' stem cells. Incompletely matched cord
blood cells are being used more frequently for transplantation in
unrelated patients. GVHD appears to be relatively less problematic with
cord blood transplantation than adult stem cell transplantation.
As a result of the encouraging results with cord blood transplants,
several organizations in the United States, Europe, Japan and other
regions have initiated programs to bank cord blood from large numbers
of newborns. It is hoped that a large inventory of banked cord blood
units from widely diverse ethnic backgrounds and HLA types will provide
grafts for those individuals for whom the traditional bone marrow
registries cannot find donors.
The legislature of the State of New Jersey has provided funding to
develop a public umbilical cord blood bank for the citizens of the
region, called the New Jersey Cord Blood Resource, to be housed at the
Coriell Institute for Medical Research in Camden. At least two
additional medical centers in the northern and southern parts of New
Jersey will be recruited to participate in the program.
Richard D. Huhn, MD
Coriell Institute for Medical Research
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So far
Rabke is doing fine. She's still teaching and is active in the theater,
one of her loves.A veteran actress - she's performed in Italy and
off-Broadway - she recently did a 10-minute monologue on her life at
the Miranda Theater in New York City. She didn't talk about her
illness, she says, but she did tell the audience, "Whatever pasta and
wine won't cure, there is no cure for."
While stem
cell transplants aren't new, what is new is their possible use as a
treatment and perhaps cure in diseases other than cancer. Currently
NJMS, Hackensack University Medical Center and Thomas Jefferson
University in Philadelphia are collaborating on a project to evaluate
the effectiveness of stem cell transplants on multiple sclerosis -
better known as MS - and lupus erythematosus. Stuart D. Cook, MD,
president of UMDNJ, and professor of neurosciences at NJMS, is one of
the neurologists involved in the project.
Pecora
explains that in these two diseases, T cells, which are part of the
white cell defense team, go awry. In MS they attack a person's own
nervous system, and in lupus they destroy connective tissue in vital
organs like the kidneys and heart.
By doing
an autologous stem cell transplant, Pecora says, the adult, rogue T
cells are destroyed and new immature T cells are born. "It's like
re-booting a computer," he says. "These new T cells haven't been
programmed to attack the nervous system and connective tissue, so it's
possible that the disease can be cured." Stem cell transplants are
being done around the country for the two diseases, and many have been
very successful.
Another
disease that may respond to the treatment is breast cancer. The news
media has portrayed it as ineffective, Pecora says, but the jury is
still out. "We need a few more years for the data to mature before
we'll know," he explains. "But there are strong indications that when
appropriately applied, it does help in certain types of breast cancer."
He
recently published a paper in the Journal of the American Medical
Association that delineates in which cases stem cell transplantation is
helpful and which ones it's not. He reported that 43 percent of young
women were still alive with no breast cancer after three years if they
were in a group that had metastatic disease, had not previously been
treated with chemotherapy, responded to chemotherapy for the disease,
and the disease was limited in the number of sites.
While stem
cell transplants are helping more people than ever before, some people
simply can't be cured. Strair says that the patients themselves,
however, are an inspiration. "In spite of all the difficulties and the
uncertainty these patients face, they all have a dignity that comes
shining through," he says. "It's people like Mrs. Rabke who keep you
going."
Both
Pecora and Strair are optimistic about the future of the therapy. Stem
cells are now being grown in the laboratory, and umbilical cord blood
has been discovered as a ready source. In fact, Pecora had two patients
in the final stages of chronic myelogenous leukemia who have survived
now for one year and two years, after a cord blood stem cell
transplant. "The number of stem cells in the cord blood was too low, so
we grew more in our lab," he says.
Strair
believes that in the not-too-distant future, cell engineering will be
another method of curing these diseases. "We hope to be able to take a
few cells from a person, manipulate them or add a gene, then give them
back and the body will cure itself."
In the
meantime, the physicians continue to research better methods of marrow
and stem cell transplantation. And with any luck at all, someday they
both may be out of business.
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