BONE MARROW TRANSPLANTATION OVERVIEW

Bone marrow transplantation (BMT), also called hematopoietic stem cell transplant or hematopoietic cell
transplant, is a type of treatment for cancer (and a few other conditions as well). A review of the normal function
of the bone marrow will help in the understanding of bone marrow transplantation.

Bone marrow function — Bone marrow is the soft, spongy area in the center of some of the larger bones of the
body. The marrow produces all of the different cells that make up the blood, such as red blood cells, white blood
cells (of many different types), and platelets. All of these cells develop from a type of precursor cell found in the
bone marrow, called a hematopoietic stem cell.

The body is able to direct hematopoietic stem cells to develop into the blood components needed at any given
moment. This is a very active process, with the bone marrow producing millions of different cells every hour. Most
of the stem cells stay in the marrow until they are transformed into the various blood components, which are then
released into the blood stream. Small numbers of stem cells, however, can be found in the circulating blood,
which allows them to be collected under certain circumstances. Various strategies can be employed to increase
the number of hematopoietic stem cells in the blood prior to collection. (See 'Peripheral blood' below.)

Bone marrow transplantation — Some of the most effective treatments for cancer, such as chemotherapy and
radiation, are toxic to the bone marrow. In general, the higher the dose, the more toxic the effects on the bone
marrow.

In bone marrow transplantation, you are given very high doses of chemotherapy or radiation therapy, which is
intended to more effectively kill cancer cells and unfortunately also destroy all the normal cells developing in the
bone marrow, including the critical stem cells. After the treatment, you must have a healthy supply of stem cells
reintroduced, or transplanted. The transplanted cells then reestablish the blood cell production process in the
bone marrow. Reduced doses of radiation or chemotherapy that do not completely destroy the bone marrow may
be used in some settings. (See 'Non-myeloablative transplant' below.)

The cells that will be transplanted can be taken from the bone marrow (called a bone marrow transplant), from
the bloodstream (called a peripheral blood stem cell transplant, which requires that you take medication to boost
the number of hematopoietic stem cells in the blood), or occasionally from blood obtained from the umbilical cord
at the time of birth of a normal newborn (called an umbilical cord blood transplant).

TYPES OF BONE MARROW TRANSPLANTATION

There are two main types of bone marrow transplantation: autologous and allogeneic.

Autologous transplant — In autologous transplantation, your own hematopoietic stem cells are removed before
the high dose chemotherapy or radiation is given, and they are then frozen for storage and later use. After your
chemotherapy or radiation is complete, the harvested cells are thawed and returned to you.

Allogeneic transplant — In allogeneic transplantation, the hematopoietic stem cells come from a donor, ideally
a brother or sister with a similar genetic makeup. If you do not have a suitably matched sibling, an unrelated
person with a similar genetic makeup may be used. Under some circumstances, a parent or child who is only
half-matched can also be used; this is termed a haploidentical transplant.

Myeloablative transplant — A myeloablative transplant uses very high doses of chemotherapy or radiation prior
to transplantation with autologous or allogeneic hematopoietic stem cells.

Non-myeloablative transplant — A non-myeloablative transplant, sometimes referred to as a "mini" or reduced

intensity transplant, allows you to have less intensive chemotherapy before transplantation with allogeneic
hematopoietic stem cells. This approach may be recommended for a variety of reasons including your age, type
of disease, other medical issues, or prior therapies.
Which type of transplant is best? — Your physician will determine whether allogeneic or autologous
transplantation is best, based on many factors including the type of cancer, your age and overall health, and the
availability of a suitable donor. As a general rule, autologous transplantation is associated with fewer serious side
effects, since you are given cells from your own body. However, an autologous transplant may be less effective
than an allogeneic transplant in treating certain kinds of cancer.

In an allogeneic transplant, the donor's immune system, which is generated from the transplanted hematopoietic
stem cells, recognize your cells, including the tumor cells, as foreign and rejects them. This beneficial reaction is
called the graft-versus-tumor effect. In many cancers, the immune response caused by the transplanted cells
improves the overall effectiveness of the treatment. This immune response helps kill off any residual cancer cells
remaining in your body.

A major concern is that you will have an immune response against normal tissues as well, called graft-versus-
host disease. (See 'Graft-versus-host disease' below.)

In a non-myeloablative transplant, it is hoped that the graft-versus-tumor effect, rather than the high-dose
chemotherapy, will help eradicate the cancer, although graft-versus-host disease is a concern (see 'Graft-versus-
host disease' below).

CHOOSING A BONE MARROW TRANSPLANT DONOR

There are many possible choices for an allogeneic hematopoietic stem cell donor. These are described below.
(See "Donor selection for hematopoietic cell transplantation".)

Matched donor — To help minimize the problems that can be caused by the expected immune response, a
donor who has similar genetic makeup to you is preferred. Your cells will seem "less foreign" to the transplanted
donor cells. Siblings (ie, brothers and sisters who share the same parents as you) are typically the only members
of your family that are tested for being a donor because they have a one in four chance of sharing genetic
characteristics with you; these characteristics are critical for your body to accept the graft. In general, parents,
children, and relatives are not suitable donors since they do not share the same parents, and therefore do not
have the same genetic material.

An exception is called a haploidentical transplant, which may be considered under certain circumstances.

Matched unrelated donor — If no siblings are available, or if testing the blood of the siblings does not reveal a
match, a matched unrelated donor may be used. The search for an appropriate donor can be accomplished using
transplant registries throughout the world.

Mismatched related donor or umbilical cord blood donor — Some patients are offered treatment with cells
from a partially matched family member (called mismatched related donor). The hematopoietic stem cell product
may be specially prepared to minimize the immune response in the patient. Another alternative is to use umbilical
cord blood, collected from a healthy newborn infant at the time of delivery; this blood is a rich source of
hematopoietic stem cells.

PRE-BONE MARROW TRANSPLANTATION PROCEDURES

Bone marrow transplantation regimens vary from one patient to another, and depend upon the type of cancer, the
treatment program used by the medical center, the clinical trial protocol (if the patient is enrolled in a clinical trial),
as well as other factors. The most common components of the bone marrow transplantation procedure are
outlined here. You should talk with your transplant team about specific details of their program. (See "Preparative
regimens for hematopoietic cell transplantation".)

Health evaluation — Before undergoing bone marrow transplantation, you will have a complete evaluation of
your health. Your complete health history is reviewed by the transplant team. Most patients also have a number
of tests.
Your mental health is reviewed because of the stress and demands of bone marrow transplantation; some
patients meet with a mental health counselor to discuss concerns and to plan coping strategies.

You will also meet with a transplant coordinator or nurse to discuss the transplant process. Because patients who
receive donor bone marrow are hospitalized for several weeks to months, it is important that you have a clear
understanding of what will happen and what services are available. Some patients prefer to have a friend or
family member accompany them, tape record the conversation with the transplant physician, or have this
information in writing so that they can review it later.

In many cases, patients undergo bone marrow transplantation while they are in remission from their underlying
disease. You may feel well going into treatment, but you should be prepared to feel poorly for a period of time.
You must understand that you will require intensive treatment and monitoring, but that there are long-term
benefits from the treatment.

Life planning — Patients who will be in the hospital for several weeks or months need to make plans regarding
their family, home, finances, pets, and employment. The National Marrow Donor Program has excellent
information about these and other bone marrow transplantation related topics.

During the pre-transplant planning process, you should consider completing an advanced directive. This is a legal
document that describes the type of care you want in case you are unable to communicate. Advance directives
include a living will, durable power of attorney, and healthcare proxy; a social worker or attorney can provide
guidance about what documents are needed. The laws surrounding these documents vary from one state to
another, so it is important to be sure the correct guidelines are used.

Central line placement — A number of medications will be required before, during, and after bone marrow
transplantation. To avoid the need for multiple intravenous lines and needle sticks, most patients will have a
central line placed before treatment begins. This requires a short surgical procedure to insert a thin, flexible
plastic tube into a large vein in the chest, above the heart. The line usually has two or three ports, which can be
used to infuse medications or blood products (including the hematopoietic stem cell product), as well as to
withdraw blood samples.

After the central line is placed, you must keep the area clean and watch for signs and symptoms of infection
(pain, redness, swelling, or fluid drainage from the site, fever or chills).

Harvesting hematopoietic stem cells — If you are having an autologous transplant, hematopoietic stem cells
will be removed from your body before intensive chemotherapy or radiation begins. The most common sources
for hematopoietic stem cells are bone marrow and blood.

Bone marrow — If your bone marrow has been invaded with cancer cells, hematopoietic stem cell removal may
be preceded by one or more courses of chemotherapy. Removal (called harvest) of bone marrow stem cells is
done while you are under general or epidural anesthesia. The harvest is done by using a long needle to
repeatedly remove a sample of bone marrow fluid from multiple areas in your pelvic and hip bones.

Peripheral blood — The harvest of peripheral blood stem cells is similar to the process of platelet donation. It
uses an apparatus, called an apheresis device, which removes hematopoietic stem cells from blood by a filtration
process. Blood is removed from a vein in one location, filtered, and then returned to a vein in another location.
The process does not require anesthesia.

In order for there to be sufficient numbers of hematopoietic stem cells in the blood, you (or the donor) must first
be treated with either chemotherapy or a growth factor that stimulates the production of hematopoietic stem cells.
Healthy donors only receive growth factor; patients with cancer may receive growth factor alone or chemotherapy
plus growth factor. The most commonly used growth factor is granulocyte colony-stimulating factor (G-CSF or
Neupogen).

Allogeneic bone marrow harvest — People who donate their bone marrow will undergo harvest the day of
transplant or one day prior. The donor is usually given general anesthesia to prevent pain.

Following the procedure, pain in the donor is usually relatively minor and can be treated with pain medications
such as acetaminophen. The donor may be hospitalized overnight following the procedure, and generally returns
to his or her prior state of health within the following one to two weeks.
Myeloablative therapy — As noted above, many patients receiving bone marrow transplantation will undergo
myeloablative therapy, which destroys bone marrow function as part of the intensive treatment for the patient's
underlying cancer. The purpose of this treatment is to reduce the amount of cancer in the body and also to
suppress the immune system adequately so that the graft will not be rejected. Depending upon the underlying
disease and other factors, this phase of treatment may involve intensive chemotherapy, total body irradiation
(radiation therapy), or both.

Preventing infection — When bone marrow function is destroyed, you are at risk for developing life-threatening
infections because you have temporarily lost your ability to produce white blood cells (the infection-fighting cells
in the blood). You are also at risk for excessive bleeding due to the reduced number of platelets in the blood.
(See "Prevention of infections in hematopoietic cell transplant recipients".)

It is important to minimize your exposure to bacteria, viruses, and fungi after myeloablative therapy because even
a small number of organisms (that are usually encountered every day) can cause serious infection.

Patients who undergo allogeneic transplant are often placed in protective isolation in a private room. The room's
air is filtered and air from the room is forced out when the door is opened (called a positive-pressure room). This
isolation, combined with feeling poorly, can be challenging to some people who may feel
depressed and/or anxious. Discussing these issues with your health care team is very important.

Special precautions are required for all persons who enter the room to reduce the chance of infection. Hand
washing is one of the most important precautions, and has been shown to significantly reduce the chance of
transmitting infection. Visitors should NOT bring fresh fruit, plants, or flowers into your room because these can
harbor microorganisms that are dangerous.

Other measures may be taken to reduce the chance of infection. For example, antibiotics,
antifungal, and/or antiparasitic medications may be given to prevent infections, and your diet may be restricted to
exclude items that contain potentially infectious organisms. For example, all foods should be cooked until hot,
raw fruits and vegetables should be avoided, and drinking water should be sterilized.

Most patients can shower. There has been a concern that showers can aerosolize fungal spores, and some
centers prefer that patients take a tub or sponge bath. You can wear a hospital gown or your own clean clothing.

Different transplant centers use different precautions and your health care team will discuss the precautions and
procedures that they expect.

Blood product transfusions — During the time that the marrow is not functioning, you will likely require
transfusion of blood products, such as red cells, which carry oxygen to the tissues, or platelets, which help
prevent bleeding. These blood products have no white blood cells and are irradiated to reduce the risk of an
immune response.

BONE MARROW TRANSPLANTATION PROCEDURE

When the intensive chemotherapy and/or radiation are complete, you will be given an infusion of the harvested
bone marrow or peripheral blood stem cells. The infusion is given through an intravenous (IV) line, usually the
central line. The infusion usually takes about an hour, and usually causes no pain.

The cells find their way to the bone marrow, where they will reestablish normal production of blood cells; this
process is called engraftment. Determining when engraftment has occurred is important because it is used to
determine when it is safe for you to go homeand/or reduce isolation procedures. Medications that stimulate the
bone marrow to produce white and red cells may be used when engraftment is slower than expected.
(See "Hematopoietic support after hematopoietic cell transplantation".)

Engraftment is measured by performing daily blood cell counts. Neutrophils are a type of white blood cell that are
a marker of engraftment; the absolute neutrophil count (ANC) must be at least 500 for three days in a row to say
that engraftment has occurred. This can occur as soon as 10 days after transplant, although 15 to 20 days is
common for patients who are given bone marrow or peripheral blood cells. Umbilical cord blood recipients usually
require between 21 and 35 days for neutrophil engraftment.

Platelet counts are also used to determine when engraftment has occurred. The platelet count must be between
20,000 and 50,000 (without a recent platelet transfusion). This usually occurs at the same time or soon after
neutrophil engraftment, but can take as long as eight weeks and even longer in some instances for people who
are given umbilical cord blood.

BONE MARROW TRANSPLANTATION SIDE EFFECTS

The high-dose chemotherapy and total body irradiation required for bone marrow transplantation can have
serious side effects. You should discuss the expected side effects, toxicities, and risks associated with bone
marrow transplant before deciding to undergo the procedure. You will be asked to sign a consent form indicating
that you have received verbal and written information to understand the risks and benefits of the proposed
treatment, possible treatment alternatives, and that all your questions have been answered.

Common side effects — Some of the most common side effects include:

●Mucositis (mouth sores) and diarrhea – Mucositis and diarrhea are caused by the damage done to rapidly
dividing cells (such as skin cells in the mouth and digestive tract) by chemotherapy and radiation. If
mucositis is severe and affects your ability to eat, intravenous nutrition (called TPN, total parenteral
nutrition) may be given. Pain medications are usually given as well.
●Nausea and vomiting – Nausea and vomiting can be prevented and treated with a combination of
medications, usually including a 5-HT3 receptor antagonist (dolasetron, granisetron, ondansetron,
tropisetron, or palonosetron), an NK1 receptor antagonist (aprepitant [Emend]), and a steroid
(dexamethasone).
●Loss of hair – Loss of hair is temporary, and generally includes hair on the head, face, and body. After
high-dose chemotherapy and radiation are completed, hair begins to regrow. No treatment is available to
prevent hair loss or speed its regrowth.
●Infertility – The risk of permanent infertility after bone marrow transplant depends upon the treatments
used (high-dose chemotherapy versus total body irradiation, ablative versus non-ablative regimen) and
dosage given. If you are of reproductive age, you should speak with your healthcare provider about options
for lowering the risks of infertility and the option of donating eggs or sperm before treatment begins.
(See "Fertility preservation in patients undergoing gonadotoxic treatment or gonadal resection".)
●Organ toxicity – The lungs, liver, and bones are at greatest risk of damage as a result of treatments used
with bone marrow transplantation. People who have total body irradiation can develop cataracts in the eyes,
although this complication is less common with current methods of delivering radiation treatment.
●Secondary cancers – There is a small risk of a second cancer developing in patients who undergo bone
marrow transplantation, probably as a result of the treatments used for the first cancer as well as the
treatments required for transplant. The second cancer usually develops several years (typically three to
five) after bone marrow transplantation. (See "Malignancy after hematopoietic cell transplantation".)

Graft-versus-host disease — Between 10 and 50 percent of patients who receive an allogeneic transplant
experience a side effect known as graft-versus-host disease (GVHD). Graft-versus-host disease is separated into
acute and chronic phases due to timing and clinical presentation. This problem does not occur following
autologous transplantation (when the patient is the donor). (See "Prevention of acute graft-versus-host disease".)

The "graft" refers to the transplanted hematopoietic stem cells; the "host" refers to the patient. Thus, graft-versus-
host disease refers to a condition in which the donor's immune cells attack some of your organs. GVHD is the
biggest single threat, other than the underlying disease, to the success of a bone marrow transplant.

Treatments are given to help prevent GVHD, and generally include immunosuppressive medications, antibiotics,
and sometimes steroids. If GVHD develops, additional treatment with high-dose steroids may lessen its severity.
Symptoms can include skin rash, diarrhea, liver damage, or other problems, depending upon the organ that is
affected. (See "Treatment of chronic graft-versus-host disease".)
Graft failure — Failure of engraftment is a rare complication that occurs in approximately one percent of cases
following bone marrow transplantation. The risk of graft failure can be higher depending upon the type of
transplant and the source of hematopoietic stem cells. Discuss these risks with the transplant team prior to
treatment. (See "Immunotherapy for the prevention and treatment of relapse following hematopoietic cell
transplantation".)

Risk of death — Bone marrow transplantation carries a risk of treatment-related death. The risk of death
depends upon your age, the nature of the underlying disease, the type of transplant (autologous or allogeneic),
and other factors, including the skill and expertise of the institution where treatment is offered. Your risk, as well
as the potential benefits of bone marrow transplantation, should be discussed with the treatment team before any
decision is made about undergoing a transplant procedure.

POST-BONE MARROW TRANSPLANTATION CARE

After engraftment occurs, blood cell counts continue to rise and the immune system becomes stronger. You will
usually be cared for by the transplant team and monitored closely for complications.

Non-myeloablative transplants may be done on an outpatient basis, allowing you to sleep at home. Other types of
transplantation require you to stay in the hospital for two to three weeks following transplantation. In all cases,
frequent visits to the healthcare provider's office are needed following discharge. If you live a distance from your
provider, you should arrange to live in a place within reasonable driving distance to the treatment center until at
least 100 days have passed since the transplant.

Patients who undergo bone marrow transplantation are at an increased risk of infection for many months
following transplantation. You should be aware of these risks and monitor yourself for symptoms of infection,
including fever (temperature greater than 100.4ºF or 38ºC), pain, or chills. You may be given antibiotics to
prevent infections.

Studies have shown that most patients who undergo transplant and remain free of cancer have a good quality of
life. Most patients are able to be active, employed, and in reasonably good health. Quality of life usually
continues to improve in the months following transplant.

CLINICAL TRIALS

A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of
known therapies, and patients who will undergo bone marrow transplantation may be asked to participate. Ask a
healthcare provider for more information about clinical trials, or read further at the following web sites.

●www.cancer.gov/clinicaltrials/
●http://clinicaltrials.gov/

Videos addressing common questions about clinical trials are available from the American Society of Clinical
Oncology (http://www.cancer.net/pre-act).

SUMMARY

●Bone marrow transplantation (BMT) is a treatment used in some types of cancer.

●Bone marrow is the soft, spongy area in the center of some of the larger bones of the body. The marrow
produces all of the different cells that make up the blood, such as red blood cells, white blood cells, and
platelets. All of these cells develop from a type of basic cell found in the bone marrow, called a stem cell.
●In bone marrow transplantation, the patient is given very high doses of chemotherapy or radiation therapy,
which kills cancer cells and destroys all the normal cells developing in the bone marrow, including the
critical stem cells. After the treatment, the patient must have a healthy supply of hematopoietic stem cells
reintroduced, or transplanted.
●There are two types of bone marrow transplantation, autologous and allogeneic. An autologous bone
marrow transplant uses a patient's own bone marrow or blood. An allogeneic bone marrow transplant uses
a donor's bone marrow or blood. The donor is usually a relative of the patient (eg, sister), although
unrelated donors are sometimes used.
●Most patients who have bone marrow transplantation must remain in the hospital for several days or
weeks during their treatment and recovery. It is important to understand and follow the hospital's bone
marrow transplantation treatment plan to minimize the risk of complications (eg, infection) and to know what
to expect in advance.
●The treatments required before and during bone marrow transplantation can have serious side effects.
Patients should be aware of the most common side effects (eg, diarrhea, nausea, vomiting, mouth sores) as
well as the types of treatments that are available to improve comfort.
●Following bone marrow transplantation, most people stay in the hospital for several weeks. However, even
after going home, frequent visits with a doctor or nurse are needed for three to six months.
●Clinical trials are carefully controlled studies of new treatments or new combinations of current treatment.
Clinical trials help researchers to learn the best way to treat specific conditions. Some patients who have
bone marrow transplantation will be asked to participate in a clinical trial.