Bone Marrow Transplantation

What is a bone marrow transplant?

Bone marrow transplant (BMT) is a special therapy for patients with certain
cancers or other diseases. A bone marrow transplant involves taking cells that
are normally found in the bone marrow (stem cells), filtering those cells, and
giving them back either to the donor (patient) or to another person. The goal of
BMT is to transfuse healthy bone marrow cells into a person after his or her
own unhealthy bone marrow has been treated to kill the abnormal cells.

Bone marrow transplant has been used successfully to treat diseases such as
leukemias, lymphomas, aplastic anemia, immune deficiency disorders, and
some solid tumor cancers since 1968.

What is bone marrow?

Bone marrow is the soft, spongy tissue found inside bones. It is where most of
the body's blood cells develop and are stored.

The blood cells that make other blood cells are called stem cells. The most
primitive of the stem cells is called the pluripotent stem cell. This is different
than other blood cells with regard to the following properties:

 Renewal. It is able to reproduce another cell identical to itself.

 Differentiation. It is able to generate one or more subsets of more
mature cells.

It is the stem cells that are needed in bone marrow transplant.

Why is a bone marrow transplant needed?

The goal of a bone marrow transplant is to cure many diseases and types of
cancer. When the doses of chemotherapy or radiation needed to cure a
cancer are so high that a person's bone marrow stem cells will be
permanently damaged or destroyed by the treatment, a bone marrow
transplant may be needed. Bone marrow transplants may also be needed if
the bone marrow has been destroyed by a disease.

A bone marrow transplant can be used to:

  Replace diseased, nonfunctioning bone marrow with healthy functioning
bone marrow (for conditions such as leukemia, aplastic anemia, and
sickle cell anemia).
 Regenerate a new immune system that will fight existing or residual
leukemia or other cancers not killed by the chemotherapy or radiation
used in the transplant.
 Replace the bone marrow and restore its normal function after high
doses of chemotherapy and/or radiation are given to treat a malignancy.
This process is often called rescue.
 Replace bone marrow with genetically healthy functioning bone marrow
to prevent more damage from a genetic disease process (such as
Hurler's syndrome and adrenoleukodystrophy).

The risks and benefits must be weighed in a thorough discussion with your
healthcare provider and specialists in bone marrow transplants before the
procedure.

What are some diseases that may benefit from bone marrow
transplant?
The following diseases are the ones that most commonly benefit from bone
marrow transplant:

 Leukemias
 Severe aplastic anemia
 Lymphomas
 Multiple myeloma
 Immune deficiency disorders
 Some solid-tumor cancers (in rare circumstances)

However, patients experience diseases differently, and bone marrow

transplant may not be right for everyone who suffers from these diseases.

What are the different types of bone marrow transplants?

There are different types of bone marrow transplants depending on who the
donor is. The different types of BMT include the following:

 Autologous bone marrow transplant. The donor is the patient

himself or herself. Stem cells are taken from the patient either by bone
marrow harvest or apheresis (a process of collecting peripheral blood
 stem cells), frozen, and then given back to the patient after intensive
treatment. Often the term rescue is used instead of transplant.
 Allogeneic bone marrow transplant. The donor shares the same
genetic type as the patient. Stem cells are taken either by bone marrow
harvest or apheresis from a genetically matched donor, usually a
brother or sister. Other donors for allogeneic bone marrow transplants
may include the following:
o A parent. A haploid-identical match is when the donor is a
parent and the genetic match is at least half identical to the
recipient. These transplants are rare.
o Unrelated bone marrow transplants (UBMT or MUD for

matched unrelated donor). The genetically matched marrow

or stem cells are from an unrelated donor. Unrelated donors are
found through national bone marrow registries.
 Umbilical cord blood transplant. Stem cells are taken from an
umbilical cord immediately after delivery of an infant. These stem cells
reproduce into mature, functioning blood cells quicker and more
effectively than do stem cells taken from the bone marrow of another
child or adult. The stem cells are tested, typed, counted, and frozen until
they are needed for a transplant.

How are a donor and recipient matched?

Matching involves typing human leukocyte antigen (HLA) tissue. The antigens
on the surface of these special white blood cells determine the genetic
makeup of a person's immune system. There are at least 100 HLA antigens;
however, it is believed that there are a few major antigens that determine
whether a donor and recipient match. The others are considered "minor" and
their effect on a successful transplant is not as well-defined.

Medical research is still investigating the role all antigens play in the process
of a bone marrow transplant. The more antigens that match, the better the
engraftment of donated marrow. Engraftment of the stem cells happens when
the donated cells make their way to the marrow and begin making new blood
cells.

Most of the genes that "code" for the human immune system are on one
chromosome. Since we only have two of each chromosome, one we received
from each of our parents, a full sibling of a patient in need of a transplant has
a 1 in 4 chance of having gotten the same set of chromosomes and being a
"full match" for transplantation.
#TomorrowsDiscoveries: Donors for Bone Marrow Transplant | Javier Bolaños-
Meade, M.D.

Dr. Javier Bolaños-Meade is working to expand the donor pool for bone
marrow transplants and reduce post-transplant complications.

The bone marrow transplant team

The group of specialists involved in the care of patients going through
transplant is often referred to as the transplant team. All individuals work
together to give the best chance for a successful transplant. The team
consists of the following:

 Healthcare providers. Healthcare providers who specialize in

oncology, hematology, immunology, and bone marrow transplantation.
 Bone marrow transplant nurse coordinator. A nurse who
organizes
all aspects of care provided before and after the transplant. The nurse
coordinator will provide patient education, and coordinates the
diagnostic testing and follow-up care.
 Social workers. Professionals who will help your family deal with many
issues that may arise, including lodging and transportation, finances,
and legal issues.
 Dietitians. Professionals who will help you meet your nutritional needs
before and after the transplant. They will work closely with you and your
family.
 Physical therapists. Professionals who will help you become strong
and independent with movement and endurance after the
transplantation.
 Pastoral care. Chaplains who provide spiritual care and support.
 Other team members. Several other team members will evaluate you
before transplantation and will give follow-up care as needed. These
include, but are not limited to, the following:
o Pharmacists
o Respiratory therapists
o Lab technicians
o Infectious disease specialists
o Dermatologists
o Gastroenterologists
o Psychologists
An extensive evaluation is completed by the bone marrow transplant team.
The decision for you to undergo a bone marrow transplant will be based on
many factors, including the following:

 Your age, overall health, and medical history

 Extent of the disease
 Availability of a donor
 Your tolerance for specific medicines, procedures, or therapies
 Expectations for the course of the disease
 Expectations for the course of the transplant
 Your opinion or preference

Preparation for the recipient

For a patient receiving the transplant, the following will occur in advance of the
procedure:

 Before the transplant, an extensive evaluation is completed by the bone

marrow transplant team. All other treatment choices are discussed and
evaluated for risk versus benefit.
 A complete medical history and physical exam are performed, including
multiple tests to evaluate the patient's blood and organ functions (for
example, heart, kidney, liver, and lungs).
 A patient will often come into the transplant center up to 10 days before
transplant for hydration, evaluation, placement of the central venous
line, and other preparations. A catheter, also called a central venous
line, is surgically placed in a vein in the chest area. Blood products and
medicines will be given through the catheter during treatment.
 For an allogeneic transplant, a suitable (tissue typed and matched)
donor must be available. Finding a matching donor can be a challenging
and lengthy process, especially if a sibling match is not available.
Voluntary marrow donors are registered in several national and
international registries. A bone marrow search involves searching these
registries for donors whose blood most closely resembles or matches
the individual needing the transplant.

Preparation for the donor

 Donor sources available include: self, sibling, parent or relative,
nonrelated person, or umbilical cord from a related or nonrelated
person. There are national and international registries for nonrelated
 people and cord blood. Some family members may be typed because of
the desire to help. These relatives may or may not elect to have their
type registered for use with other recipients.
 If the potential donor is notified that he or she may be a match for a
patient needing a transplant, he or she will undergo additional tests.
Tests related to his or her health, exposure to viruses, and genetic
analysis will be done to determine the extent of the match. The donor
will be given instructions on how a bone marrow donation will be
made.
 Once a match for a patient needing a bone marrow transplant is found,
then stem cells will be collected either by a bone marrow harvest. This
is a collection of stem cells with a needle placed into the soft center of
the bone marrow. Or by a peripheral blood stem cell collection. This is
where stem cells are collected from the circulating cells in the blood. Of
the two, peripheral blood stem cell donations are now more common.
Cord blood has already been collected at the time of a birth and stored
for later use.

How are the stem cells collected?

A bone marrow transplant is done by transferring stem cells from one person
to another. Stem cells can either be collected from the circulating cells in the
blood (the peripheral system) or from the bone marrow.

 Peripheral blood stem cells. Peripheral blood stem cells (PBSCs) are
collected by apheresis. This is a process in which the donor is
connected to a special cell separation machine via a needle inserted in
arm veins. Blood is taken from one vein and is circulated though the
machine which removes the stem cells and returns the remaining blood
and plasma back to the donor through another needle inserted into the
opposite arm. Several sessions may be needed to collect enough stem
cells to ensure a chance of successful engraftment in the recipient.

A medicine may be given to the donor for about one week prior to apheresis
that will stimulate the bone marrow to increase production of new stem cells.
These new stem cells will be released from the marrow and into the circulating
or peripheral blood system; from there they can be collected during apheresis.

 Bone marrow harvest. Bone marrow harvesting involves collecting

stem cells with a needle placed into the soft center of the bone, the
marrow. Most sites used for bone marrow harvesting are located in the
hip bones and the sternum. The procedure takes place in the operating
 room. The donor will be anesthetized during the harvest and will not feel
the needle. In recovery, the donor may experience some pain in the
areas where the needle was inserted.

If the donor is the person himself or herself, it is called an autologous bone

marrow transplant. If an autologous transplant is planned, previously
collected stem cells, from either peripheral (apheresis) or harvest, are
counted, screened, and ready to infuse.

The bone marrow transplant procedure

The preparations for a bone marrow transplant vary depending on the type of
transplant, the disease needing transplant, and your tolerance for certain
medicines. Consider the following:

 Most often, high doses of chemotherapy and/or radiation are included in

the preparations. This intense therapy is required to effectively treat the
malignancy and make room in the bone marrow for the new cells to
grow. This therapy is often called ablative, or myeloablative, because of
the effect on the bone marrow. The bone marrow produces most of the
blood cells in our body. Ablative therapy prevents this process of cell
production and the marrow becomes empty. An empty marrow is
needed to make room for the new stem cells to grow and establish a
new blood cell production system.
 After the chemotherapy and/or radiation is administered, the marrow
transplant is given through the central venous catheter into the
bloodstream. It is not a surgical procedure to place the marrow into the
bone, but is similar to receiving a blood transfusion. The stem cells find
their way into the bone marrow and begin reproducing and growing
new, healthy blood cells.
 After the transplant, supportive care is given to prevent and treat
infections, side effects of treatments, and complications. This includes
frequent blood tests, close monitoring of vital signs, strict measurement
of fluid input and output, daily weigh-ins, and providing a protected and
clean environment.

The days before transplant are counted as minus days. The day of transplant
is considered day zero. Engraftment and recovery following the transplant are
counted as plus days. For example, a patient may enter the hospital on day -8
for preparative regimen. The day of transplant is numbered zero. Days +1, +2,
etc., will follow. There are specific events, complications, and risks associated
with each day before, during, and after transplant. The days are numbered to
help the patient and family understand where they are in terms of risks and
discharge planning.

During infusion of bone marrow, the patient may experience the following:

 Pain
 Chills
 Fever
 Hives
 Chest pain

After infusion, the patient may:

 Spend several weeks in the hospital

 Be very susceptible to infection
 Experience excessive bleeding
 Need blood transfusions
 Be confined to a clean environment
 Take multiple antibiotics and other medicines
 Be given medicine to prevent graft-versus-host disease—if the
transplant was allogeneic. The transplanted new cells (the graft) tend to
attack the patient's tissues (the host), even if the donor is a relative.
 Undergo continual laboratory testing
 Experience nausea, vomiting, diarrhea, mouth sores, and extreme
weakness
 Experience temporary mental confusion and emotional or psychological
distress

After leaving the hospital, the recovery process continues for several months
or longer, during which time the patient cannot return to work or many
previously enjoyed activities. The patient must also make frequent follow-up
visits to the hospital or healthcare provider's office.

When does engraftment happen?

Engraftment of the stem cells happens when the donated cells make their way
to the marrow and begin making new blood cells. Depending on the type of
transplant and the disease being treated, engraftment usually happens around
day +15 or +30. Blood counts will be checked often during the days following
transplant to evaluate initiation and progress of engraftment. Platelets are
generally the last blood cell to recover.
Engraftment can be delayed because of infection, medicines, low donated
stem cell count, or graft failure. Although the new bone marrow may begin
making cells in the first 30 days following transplant, it may take months, even
years, for the entire immune system to fully recover.

What complications and side effects may happen following

BMT?
Complications may vary, depending on the following:

 Type of marrow transplant

 Type of disease requiring transplant
 Preparative regimen
 Age and overall health of the recipient
 Variance of tissue matching between donor and recipient
 Presence of severe complications

The following are complications that may happen with a bone marrow
transplant. However, each individual may experience symptoms differently.
These complications may also happen alone, or in combination:

 Infections. Infections are likely in the patient with severe bone marrow
suppression. Bacterial infections are the most common. Viral and fungal
infections can be life-threatening. Any infection can cause an extended
hospital stay, prevent or delay engraftment, and/or cause permanent
organ damage. Antibiotics, antifungal medicines, and antiviral medicines
are often given to try to prevent serious infection in the
immunosuppressed patient.
 Low platelets and low red blood cells. Thrombocytopenia (low
platelets) and anemia (low red blood cells), as a result of a
nonfunctioning bone marrow, can be dangerous and even life-
threatening. Low platelets can cause dangerous bleeding in the lungs,
gastrointestinal (GI) tract, and brain.
 Pain. Pain related to mouth sores and gastrointestinal (GI) irritation is
common. High doses of chemotherapy and radiation can cause severe
mucositis (inflammation of the mouth and GI tract).
 Fluid overload. Fluid overload is a complication that can lead to
pneumonia, liver damage, and high blood pressure. The main reason
for fluid overload is because the kidneys cannot keep up with the large
amount of fluid being given in the form of intravenous (IV) medicines,
 nutrition, and blood products. The kidneys may also be damaged from
disease, infection, chemotherapy, radiation, or antibiotics.
 Respiratory distress. Respiratory status is an important function that
may be compromised during transplant. Infection, inflammation of the
airway, fluid overload, graft-versus-host disease, and bleeding are all
potential life-threatening complications that may happen in the lungs
and pulmonary system.
 Organ damage. The liver and heart are important organs that may be
damaged during the transplantation process. Temporary or permanent
damage to the liver and heart may be caused by infection, graft-versus-
host disease, high doses of chemotherapy and radiation, or fluid
overload.
 Graft failure. Failure of the graft (transplant) taking hold in the marrow
is a potential complication. Graft failure may happen as a result of
infection, recurrent disease, or if the stem cell count of the donated
marrow was insufficient to cause engraftment.
 Graft-versus-host disease. Graft-versus-host disease (GVHD) can be
a serious and life-threatening complication of a bone marrow transplant.
GVHD occurs when the donor's immune system reacts against the
recipient's tissue. As opposed to an organ transplant where the patient's
immune system will attempt to reject only the transplanted organ, in
GVHD the new or transplanted immune system can attack the entire
patient and all of his or her organs. This is because the new cells do not
recognize the tissues and organs of the recipient's body as self. Over
time and with the help of medicines to suppress the new immune
system, it will begin to accept its new body and stop attacking it. The
most common sites for GVHD are GI tract, liver, skin, and lungs.

Long-term outlook for a bone marrow transplantation

Prognosis greatly depends on the following:

 Type of transplant
 Type and extent of the disease being treated
 Disease response to treatment
 Genetics
 Your age and overall health
 Your tolerance of specific medicines, procedures, or therapies
 Severity of complications
As with any procedure, in bone marrow transplant the prognosis and long-
term survival can vary greatly from person to person. The number of
transplants being done for an increasing number of diseases, as well as
ongoing medical developments, have greatly improved the outcome for bone
marrow transplant in children and adults. Continuous follow-up care is
essential for the patient following a bone marrow transplant. New methods to
improve treatment and to decrease complications and side effects of a bone
marrow transplant are continually being discovered.