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 their 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 the medium for development and storage of most 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 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. This is commonly done 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 (for diseases, such as lymphoma and neuroblastoma).
- 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 doctor and specialists in bone marrow transplants prior to procedure.
What are some diseases that may benefit from a bone marrow transplant?
The following diseases are the ones that most commonly benefit from bone marrow transplant:
- Severe aplastic anemia
- Multiple myeloma
- Immune deficiency disorders
- Some solid-tumor cancers
However, patients experience diseases differently, and bone marrow transplant may not be appropriate for everyone who suffers from these diseases.
What are the different types of bone marrow transplant?
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: 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.
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 occurs when the donated cells make their way to the marrow and begin producing new blood cells. Most of the genes that "code" for the human immune system are on one chromosome. A full sibling of a patient in need of a transplant has a one-in-four chance of having gotten the same set of chromosomes and being a "full match" for transplantation.
How are 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 a apheresis, 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 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; 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. What is 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 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:
- 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 medications
- Be given medication 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 doctor's office.
When does engraftment occur?
Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin producing 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 checked 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 transplant. 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 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 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: Failure of the graft (transplant) taking hold in the marrow 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. 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.
What is the long-term outlook for a bone marrow transplant?
Prognosis greatly depends on the following:
- Type of transplant
- Type and extent of the disease being treated
- Disease response to treatment
- Your age and overall health
- Your tolerance of specific medications, 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.