The Nuts and Bolts of Bone
Marrow Transplants
Bone marrow transplantation (BMT) is a relatively
new medical procedure being used to treat diseases once thought
incurable. Since its first successful use in 1968, BMTs have
been used to treat patients diagnosed with leukemia, aplastic
anemia, lymphomas such as Hodgkin's disease, multiple myeloma,
immune deficiency disorders and some solid tumors such as breast
and ovarian cancer.
In 1991, more than 7,500 people underwent BMTs
nationwide. Although BMTs now save thousands of lives each year,
70 percent of those needing a BMT using donor marrow are unable
to have one because a suitable bone marrow donor cannot be found.
WHAT IS BONE MARROW?
Bone marrow is a spongy tissue found inside bones.
The bone marrow in the breast bone, skull, hips, ribs and spine
contains stem cells that produce the body's blood cells. These
blood cells include white blood cells (leukocytes), which fight
infection; red blood cells (erythrocytes), which carry oxygen
to and remove waste products from organs and tissues; and platelets,
which enable the blood to dot
WHY TRANSPLANT?
In patients with leukemia, aplastic anemia, and
some immune deficiency diseases, the stem cells in the bone
marrow malfunction, producing an excessive number of defective
or immature blood cells (in the case of leukemia) or low blood
cell counts (in the case of aplastic anemia). The immature or
defective blood cells interfere with the production of normal
blood cells, accumulate in the bloodstream and may invade other
tissues.
Large doses of chemotherapy and/or radiation
are required to destroy the abnormal stem cells and abnormal
blood cells. These therapies, however, not only kill the abnormal
cells but can destroy normal cells found in the bone marrow
as well. Similarly, aggressive chemotherapy used to treat some
lymphomas and other cancers can destroy healthy bone marrow.
A bone marrow transplant enables physicians to treat these diseases
with aggressive chemotherapy and/or radiation by allowing replacement
of the diseased or damaged bone marrow after the chemotherapy/radiation
treatment.
While bone marrow transplants do not provide
100 percent assurance that the disease will not recur, a transplant
can increase the likelihood of a cure or at least prolong the
period of disease-free survival for many patients.
TYPES OF TRANSPLANTS
In a bone marrow transplant, the patient's diseased
bone marrow is destroyed and healthy marrow is infused into
the patient's blood-stream. In a successful transplant, the
new bone marrow migrates to the cavities of the large bones,
engrafts and begins producing normal blood cells.
If bone marrow from a donor is used, the transplant
is called an "allogeneic" BMT, or "syngeneic"
BMT if the donor is an identical twin. In an allogeneic BMT,
the new bone marrow infused into the patient must match the
genetic makeup of the patient's own marrow as perfectly as possible.
Special blood tests are conducted to determine whether or not
the donor's bone marrow matches the patient's. If the donor's
bone marrow is not a good genetic match, it will perceive the
patient's body as foreign material to be attacked and destroyed.
This condition is known as graft-versus-host disease (GVHD)
and can be life-threatening. Alternatively, the patient's immune
system may destroy the new bone marrow. This is called graft
rejection.
There is a 35 percent chance that a patient will
have a sibling whose bone marrow is a perfect match. If the
patient has no matched sibling, a donor may be located in one
of the international bone marrow donor registries, or a mis-matched
or autologous transplant may be considered.
In some cases, patients may be their own bone
marrow donors. This is called an autologous BMT and is possible
if the disease afflicting the bone marrow is in remission or
if the condition being treated does not involve the bone marrow
(e.g. breast cancer, ovarian cancer, Hodgkin's disease, non-Hodgkin's
lymphoma, and brain tumors). The bone marrow is extracted from
the patient prior to transplant and may be "purged"
to remove lingering malignant cells (if the disease has afflicted
the bone marrow).
PREPARING FOR THE TRANSPLANT
A successful transplant requires the patient be
healthy enough to undergo the rigors of the transplant procedure.
Age, general physical condition, the patient's diagnosis and
the stage of the disease are all considered by the physician
when determining whether a person should undergo a transplant.
Prior to a bone marrow transplant, a battery
of tests is carried out to ensure the patient is physically
capable of undergoing a transplant. Tests of the patient's heart,
lung, kidney and other vital organ functions are also used to
develop a patient "baseline" against which post-transplant
tests can be compared to determine if any body functions have
been impaired. The pre-transplant tests are usually done on
an outpatient basis.
A successful bone marrow transplant requires
an expert medical team - doctors, nurses, and other support
staff - who are experienced in bone marrow transplants, can
promptly recognize problems and emerging side effects, and know
how to react swiftly and properly if problems do arise. A good
bone marrow transplant program will also recognize the importance
of providing patients and their families with emotional and
psychological support before, during and after the transplant,
and will make personal and other support systems readily available
to families for this purpose.
BONE
MARROW HARVEST
Regardless of whether the patient or a donor
provides the bone marrow used in the transplant, the procedure
used to collect the marrow - the bone marrow harvest - is the
same. The bone marrow harvest takes place in a hospital operating
room, usually under general anesthesia. It involves little risk
and minimal discomfort.
While the patient is under anesthesia, a needle
is inserted into the cavity of the rear hip bone or "iliac
crest" where a large quantity of bone marrow is located.
The bone marrow a thick, red liquid - is extracted with a needle
and syringe. Several skin punctures on each hip and multiple
bone punctures are usually required to extract the requisite
amount of bone marrow. There are no surgical incisions or stitches
involved - only skin punctures where the needle was inserted.
The amount of bone marrow harvested depends on
the size of the patient and the concentration of bone marrow
cells in the donor's blood. Usually one to two quarts of marrow
and blood are harvested. While this may sound like a lot, it
really only represents about 2% of a person's bone marrow, which
the body replaces in four weeks.
When the anesthesia wears off, the donor may
feel some discomfort at the harvest site. The pain will be similar
to that associated with a hard fall on the ice and can usually
be controlled with Tylenol. Donors who are not also the BMT
patient are usually discharged after an overnight stay and can
fully resume normal activities in a few days.
For autologous transplants, the harvested bone
marrow will be frozen (cryopreserved) and stored at a temperature
between -80 and -196 degrees centigrade until the day of transplant.
It may first be "purged" to remove residual cancerous
cells that can't be easily identified under the microscope (see
page 30).
In allogeneic BMTs, the bone marrow may be treated
to remove "T-cells" (T cell depletion) to reduce the
risk of graft-versus-host disease (see page 94). It will then
be transferred directly to the patient's room for infusion.
PREPARATIVE REGIMEN
A patient admitted to the bone marrow transplant
unit will first undergo several days of chemotherapy and/or
radiation which destroys bone marrow and cancerous cells and
makes room for the new bone marrow. This is called the conditioning
or preparative regimen. The exact regimen of chemotherapy and/or
radiation varies according to the disease being treated and
the "protocol" or preferred treatment plan of the
facility where the BMT is being performed.
Prior to conditioning, a small flexible tube
called a catheter (sometimes called a "Hickman®" or
central venous line) will be inserted into a large vein in the
patient's chest just above the heart. This tube enables the
medical staff to administer drugs and blood products to the
patient painlessly, and to withdraw the hundreds of blood samples
required during the course of treatment without inserting needles
into the patient's arms or hands.
The dosage of chemotherapy and/or radiation given
to patients during conditioning is much stronger than dosages
administered to patients with the same disease who are not undergoing
a BMT. Patients may become weak, irritable and nauseous. Most
BMT centers administer anti-nausea medications to minimize discomfort.
THE
TRANSPLANT
A day or two following the chemotherapy and/or
radiation treatment, the transplant will occur. The bone marrow
is infused into the patient intravenously in much the same way
that any blood product is given. The transplant is not a surgical
procedure. It takes place in the patient's room, not an operating
room.
Patients are checked frequently for signs of
fever, chills, hives and chest pains while the bone marrow is
being infused. When the transplant is completed, the days and
weeks of waiting begin.
ENGRAFTMENT
The two to four weeks immediately following transplant
are the most critical. The high-dose chemotherapy and/or radiation
given to the patient during conditioning will have destroyed
the patient's bone marrow, crippling the body's "immune"
or defense system. As the patient waits for the transplanted
bone marrow to migrate to the cavities of the large bones, set
up housekeeping or "engraft," and begin producing
normal blood cells, he or she will be very susceptible to infection
and excessive bleeding. Multiple antibiotics and blood transfusions
will be administered to the patient to help prevent and fight
infection. Transfusions of platelets will be given to prevent
bleeding. Allogeneic patients will receive additional medications
to prevent and control graft-versus-host disease.
Extraordinary precautions will be taken to minimize
the patient's exposure to viruses and bacteria. Visitors and
hospital personnel will wash their hands with antiseptic soap
and, in some cases, wear protective gowns, gloves and/or masks
while in the patient's room. Fresh fruits, vegetables, plants
and cut flowers will be prohibited in the patient's room since
they often carry fungi and bacteria that pose a risk of infection.
When leaving the room, the patient may wear a mask, gown and
gloves as a barrier against bacteria and virus, and as a reminder
to others that he or she is susceptible to infection. Blood
samples will be taken daily to determine whether or not engraftment
has occurred and to monitor organ function. When the transplanted
bone marrow finally engrafts and begins producing normal blood
cells, the patient will gradually be taken off the antibiotics,
and blood and platelet transfusions will generally no longer
be required. once the bone marrow is producing a sufficient
number of healthy red blood cells, white blood cells and platelets,
the patient will be discharged from the hospital, provided no
other complications have developed. BMT patients typically spend
four to eight weeks in the hospital.
WHAT A PATIENT FEELS DURING THE
TRANSPLANT
A bone marrow transplant is a physically, emotionally,
and psychologically taxing procedure for both the patient and
family. A patient needs and should seek as much help as possible
to cope with the experience. "Toughing it out" on
your own is not the smartest way to cope with the transplant
experience.
The bone marrow transplant is a debilitating
experience. Imagine the symptoms of a severe case of the flu
- nausea, vomiting, fever, diarrhea, extreme weakness. Now imagine
what it's like to cope with the symptoms not just for several
days, but for several weeks. That approximates what a BMT patient
experiences during hospitalization.
During this period the patient will feel very
sick and weak. Walking, sitting up in bed for long periods of
time, reading books, talking on the phone, visiting with friends
or even watching TV may require more energy than the patient
has to spare.
Complications can develop after a bone marrow
transplant such as infection, bleeding, graft-versus-host disease,
or liver disease, which can create additional discomfort. The
pain, however, is usually controllable by medication. In addition,
mouth sores can develop that make eating and swallowing uncomfortable.
Temporary mental confusion sometimes occurs and can be quite
frightening for the patient who may not realize it's only temporary.
The medical staff will help the patient deal with these problems.
HANDLING EMOTIONAL STRESS
In addition to the physical discomfort associated
with the transplant experiance there is emotional and psychological
discomfort as well. Some patients find the emotional and psychological
stress more problematic than the physical discomfort.
The psychological and emotional stress stems
from several factors. First, patients undergoing transplants
are already traumatized by the news that they have a life-threatening
disease. While the transplant offers hope for their recovery,
the prospect of undergoing a long, arduous medical procedure
is still not pleasant and there's no guarantee of success.
Second, patients undergoing a transplant can
feel quite isolated. The special precautions taken to guard
against infection while the immune system is impaired can leave
a patient feeling detached from the rest of the world and cut
off from normal human contact. The patient is housed in a private
room, sometimes with special air-filtering equipment to purify
the air. The number of visitors is restricted and visitors are
asked to wear gloves, masks and/or other protective clothing
to inhibit the spread of bacteria and virus while visiting the
patient. When the patient leaves the room, he or she may be
required to wear a protective mask, gown and/or gloves as a
barrier against infection. This feeling of isolation comes at
the very time in a patient's life when familiar surroundings
and close physical contact with family and friends are most
needed.
'Helplessness" is also a common feeling
among bone marrow transplant patients, which can breed further
feelings of anger or resentment. For many, it's unnerveing to
be totally dependent on strangers for survival, no matter how
competent they may be. The fact that most patients are unfamiliar
with the medical jargon used to describe the transplant procedure
compounds the feeling of helplessness. Some also find it embarrassing
to be dependent on strangers for help with basic daily functions
such as using the washroom.
The long weeks of waiting for the transplanted
marrow to engraft, for blood counts to return to safe levels,
and for side effects to disappear increase the emotional trauma.
Recovery can be like a roller coaster ride: one day a patient
may feel much better, only to awake the next day feeling as
sick as ever.
LEAVING THE HOSPITAL
After being discharged from the hospital, a patient
continues recovery at home (or at lodging near the transplant
center if the patient is from out of town) for two to four months.
Patients usually cannot return to full-time work for up to six
months after the transplant.
Though patients will be well enough to leave
the hospital, their recovery will be far from over. For the
first several weeks the patient may be too weak to do much more
than sleep, sit up, and walk a bit around the house. Frequent
visits to the hospital or associated clinic will be required
to monitor the patient's progress, and to administer any medications
and/or blood products needed. It can take six months or more
from the day of transplant before a patient is ready to fully
resume normal activities.
During this period, the patient's white blood
cell counts are often too low to provide normal protection against
the viruses and bacteria encountered in everyday life. Contact
with the general public is therefore restricted. Crowded movie
theaters, grocery stores, department stores, etc. are places
recovering BMT patients avoid during their recuperation. Often
patients will wear protective masks when venturing outside the
home.
A patient will return to the hospital or clinic
as an outpatient several times a week for monitoring, blood
transfusions, and administration of other drugs as needed. Eventually,
the patient becomes strong enough to resume a normal routine
and to look forward to a productive, healthy life.
LIFE AFTER TRANSPLANT
It can take as long as a year for the new bone
marrow to function normally. Patients are closely monitored
during this time to identify any infections or complications
that may develop.
Life after transplant can be both exhilarating
and worrisome. On the one hand, it's exciting to be alive after
being so close to death. Most patients find their quality of
life improved after transplant.
Nonetheless, there is always the worry that relapse
will occur. Furthermore, innocent statements or events can sometimes
conjure up unpleasant memories of the transplant experience
long after the patient has recovered. It can take a long time
for the patient to come to grips with these difficulties.
IS IT WORTH IT?
Yes! For most patients contemplating a bone marrow
transplant, the alternative is near-certain death. Despite the
fact that the transplant can be a trying experience, most find
that the pleasure that comes from being alive and healthy after
the transplant is well worth the effort.
By
BMT Newsletter
