Cancer Types - Bone Marrow Transplantation

Bone Marrow Transplantation

What is a bone marrow transplantation?

Bone marrow transplantation (BMT) is a special therapy for patients with cancer or other diseases which affect the bone marrow. 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 patient or to another person. The goal of BMT is to transfuse healthy bone marrow cells into a person after their own unhealthy bone marrow has been eliminated.

Bone marrow transplantation 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 the medium for development and storage of about 95 percent of the body's blood cells.

The blood cells that produce other blood cells are called stem cells. The most primitive of the stem cells is called the pluripotent stem cell, which is different than other blood cells with regards 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 transplantation.

Why is a bone marrow transplant needed?

The goal of a bone marrow transplant is to cure many diseases and types of cancer. When a person's bone marrow has been damaged or destroyed due to a disease or intense treatments of radiation or chemotherapy for cancer, a marrow transplant may be needed.

A bone marrow transplant can be used to:

• replace diseased, non-functioning bone marrow with healthy functioning bone marrow (for conditions such as leukemia, aplastic anemia, and sickle cell anemia).
• replace the bone marrow and restore its normal function after high doses of chemotherapy or radiation are given to treat a malignancy. This process is often called "rescue" (for diseases such as lymphoma, neuroblastoma, and breast cancer).
• replace bone marrow with genetically healthy functioning bone marrow to prevent further 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 physician and physicians that specialize in bone marrow transplants prior to procedure.

What are some diseases that may benefit from bone marrow transplantation?

The following diseases are the ones that most commonly benefit from bone marrow transplantation:

• leukemias
• severe aplastic anemia
• lymphomas
• multiple myeloma
• immune deficiency disorders
• solid-tumor cancers, such as breast or ovarian

However, patients experience diseases differently, and bone marrow transplantation may not be appropriate 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 bone marrow transplant include the following:

• autologous bone marrow transplant
  The donor is the patient him/herself. Stem cells are taken from the patient either by bone marrow harvest or apheresis (peripheral blood stem cells) 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 (peripheral blood stem cells) from a genetically-matched donor, usually a brother or sister. Other donors for allogeneic bone marrow transplants include the following:
  • 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.
  • an identical twin - a syngeneic transplant is an allogeneic transplant from an identical twin. Identical twins are considered a complete genetic match for a marrow transplant.
  • 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 the 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 ready to be transplanted.

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 make-up 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 occurs when the donated cells make their way to the marrow and begin reproducing new blood cells.

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 provide the best chance for a successful transplant. The team consists of the following:

• physicians - physicians 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 provide follow-up care as needed. These include, but are not limited to, the following:
  • pharmacists
  • respiratory therapists
  • lab technicians
  • infectious disease specialists
  • dermatologists
  • gastroenterologists
  • 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 medications, 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:

• Prior to the transplant, an extensive evaluation is completed by the bone marrow transplant team. All other treatment options are discussed and evaluated for risk versus benefit.
• A complete medical history and physical examination are performed, including multiple tests to evaluate the patient's blood and organ functions (i.e., heart, kidney, liver, lungs).
• A patient will often come into the transplant center up to 10 days prior to 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 medications will be administered through the catheter.
• A suitable (tissue typed and matched) donor must be available. Finding a matching donor can be a challenging and lengthy process. 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, non-related person, or umbilical cord from a related or non-related person. There are national and international registries for non-related persons and cord blood. For family members, they 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 they may be a match for a patient needing a transplant, they will undergo additional tests. Tests related to their health, exposure to viruses, and complete 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 (collection of stem cells with a needle placed into the soft center of the bone marrow) or peripheral blood stem cell collection (stem cells are collected from the circulating cells in the blood). 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 (PBSCs)
  Peripheral blood stem cells (PBSCs) are collected by apheresis, a process in which the donor is connected to a special cell separation machine via a needle inserted in the vein. 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 required to collect enough stem cells to ensure a chance of successful engraftment in the recipient.

  A medication 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.
  

• 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 him/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 requiring transplant, and your tolerance for certain medications. 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 all 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 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 establishing new, healthy blood cells.
• 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 input and output, daily weigh-ins, and providing a protected and sterile 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.
• have blood transfusions.
• be confined to a sterile environment.
• take multiple antibiotics and other medications.
• be given medication to prevent graft-versus-host disease - if the transplantation was allogeneic. The transplanted new cells (the graft), tend to attack the patient's tissues (the host), even though the donor is a relative, such as a brother, sister, or parent.
• 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 physician's office.

When does engraftment occur?

Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin reproducing new blood cells. Depending on the type of transplant and the disease being treated, engraftment usually occurs around day +15 or +30. Blood counts will be performed frequently 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, medications, 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 occur 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 occur with a bone marrow transplantation. However, each individual may experience symptoms differently. These complications may also occur 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, anti-fungal medications, and anti-viral medications are often given 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 non-functioning bone marrow, can be dangerous and even life threatening. Low platelets can cause dangerous bleeding in the lungs, gastrointestinal (GI), 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 primary 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) medications, 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 occur 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
  Graft failure is a potential complication. Graft failure may occur 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. The new cells do not recognize the tissues and organs of the recipient’s body. 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 marrow transplant
• type and extent of the disease being treated
• disease response to treatment
• genetics
• your age and overall health
• your tolerance of specific medications, procedures, or therapies
• severity of complications

As with any procedure, such as bone marrow transplant, prognosis, and long-term survival can vary greatly from person to person. The number of transplants occurring for an increased number of diseases and medical developments has 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.

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