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Bone marrow transplantation

Note: The section below describes the process and benefits of transplantation.

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 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 transplantation and they can be collected in one of three ways:

Bone marrow: Stem cells were originally collected from the bone marrow — this is how the name “bone marrow transplant” came about. Bone marrow is collected from the iliac crest (hip bone) in the VCUHS operating room. The procedure is called a bone marrow transplant.

Blood stream: Stem cells in the bone marrow are stimulated by a special injection (growth factor) that causes the cells to be released into the blood where they can then be collected. Stem cells are collected from the blood via a procedure called apheresis, and this type of transplant is called a peripheral blood stem cell transplant.

Umbilical cord: Stem cells can also be collected and stored from the umbilical cord of a newborn baby. The use of these cells is called umbilical stem cell transplant.

What is bone marrow transplantation (BMT)?

Bone marrow transplantation is a special therapy for patients with cancer or other diseases that affect the bone marrow. A bone marrow transplant involves taking cells that are normally found in the bone marrow (stem cells) and giving them back to the patient. The goal of BMT is to transfuse healthy bone marrow cells into a person after his/her own unhealthy bone marrow has been eliminated.

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

Why is a transplant needed?

The goal of BMT 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 bone 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 other physicians who specialize in bone marrow transplants prior to the procedure.

What are some diseases that may benefit from BMT?

The following diseases are the ones that most commonly benefit from BMT:

  • Leukemias
  • Severe aplastic anemia
  • Lymphomas
  • Multiple myeloma
  • Immune deficiency disorders

However, patients experience diseases differently, and BMT 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 the donor. The different types include the following:

  • Autologous bone marrow transplant – The donor is the patient. 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:
    • 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, usually 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 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
  • Oncology nurse practitioners/physician’s assistants – advanced practitioners who are specially educated in caring for cancer patients practice with oncologists and diagnose and treat the symptoms of cancer and cancer-treatment side effects; they play a key role in guiding cancer patients through their cancer journey
  • Bone marrow transplant nurse coordinators – nurses who organize all aspects of care provided before and after the transplant, including patient education, and coordinate 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:
    • Pharmacists
    • Respiratory therapists
    • Lab technicians
    • Infectious disease specialists
    • Dermatologists
    • Gastroenterologists
    • Psychologists
    • Research coordinators

The bone marrow transplant team completes an extensive evaluation. 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:

  • An extensive evaluation including the discussion of all other treatment options and their risks and benefits
  • A complete medical history and physical examination, including multiple tests to evaluate the patient’s blood and organ functions (i.e., heart, kidney, liver, lungs)
  • An EPA catheter, also called a central venous line, is surgically placed in a vein in the chest area in order to administer blood products and medications
  • A suitable (tissue-typed and -matched) donor must be available

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 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 he or she may be a match for a patient needing a transplant, he or she will undergo additional tests. Tests related to the donor’s health, exposure to viruses and more complete HLA testing will be done to determine the extent of the match. The donor will receive instructions on how a bone marrow donation will be made.
  • Once a potential donor has been found to be suitable and agrees to proceed, 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). If a cord blood transplant is planned, the cord will be obtained from a cord blood bank.

How are the stem cells collected?

  • Peripheral blood stem cells – collected by apheresis, a process in which the donor is connected to a special cell separation machine via a needle inserted in the vein or central venous catheter. Blood is taken from one vein and is circulated though the machine that removes the stem cells and returns the remaining blood and plasma back to the donor through another needle inserted into the opposite arm or the catheter. Several sessions may be required to collect enough stem cells to ensure a chance of successful engraftment in the recipient. Medication (growth factor) is given to the donor for a few days 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 – takes place in the operating room. The physician uses a needle to remove marrow from the center of the bone (usually the hip bones). 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.
  • 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.

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 or stem cell 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, including 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:

  • Chills
  • Fever
  • Hives
  • Chest pain
  • Diarrhea

After transplant the patient may:

  • Spend several weeks in the hospital
  • Be very susceptible to infection
  • Experience excessive bleeding
  • Have blood transfusions
  • Be confined to a protected 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 regular 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 must make frequent follow-up visits to the BMT Clinic and remain near the hospital as instructed by medical staff.

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 between day +15 and day +30. Blood counts will be performed frequently during the days following transplant to evaluate engraftment. 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.

About transplantation

Bone marrow molecules

In the bone marrow, there is approximately one stem cell in every 100,000 blood cells. The bone marrow in the breast bone, skull, hips, ribs and spine contains the stem cells.

In the blood stream, the number of stem cells is about 1/100 of that in the bone marrow. Transplantation of these stem cells from the blood stream is sometimes used in addition to, or instead of, traditional bone marrow transplantation.

Stem cell transplantation differs from traditional bone marrow transplantation only in the method by which the stem cells are harvested for infusion into the patient.
Harvesting stem cells from bone marrow requires a surgical procedure.

Harvesting stem cells from the blood stream is accomplished by a process called apheresis. The patient is connected to a cell separation machine via a needle in each arm. Blood is taken from one arm, circulated through the machine to remove the stem cells, and the remaining blood cells are returned to the patient through the other arm.

Several sessions of up to six hours are required to harvest, through apheresis, enough stem cells for transplantation.

The patient undergoes all other activities, complications or side effects, and recovery period that are involved in traditional bone marrow transplantation.

Side effects

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
  • Tissue matching between donor and recipient

The following complications may occur with bone marrow transplantation. However, each individual may experience symptoms differently. These complications may occur alone, or in combination:

  • Infections – 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 nonfunctioning bone marrow, can be dangerous and even life threatening. Low platelets can cause dangerous bleeding in the lungs, gastrointestinal system or brain.
  • Pain – related to mouth sores and gastrointestinal irritation is common. High doses of chemotherapy and radiation can cause severe mucositis (inflammation of the mouth and GI tract).
  • Fluid overload – 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 medications, nutrition and blood products. The kidneys also may be damaged from disease, infection, chemotherapy, radiation or antibiotics.
  • Respiratory distress – 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 – a potential complication. Graft failure may occur as a result of infection, recurrent disease or if the donated marrow is insufficient to cause engraftment.
  • Graft-versus-host disease – can be a serious and life-threatening complication of an allogeneic bone marrow transplant. GVHD occurs when the donor’s immune system reacts against the recipient’s tissue. The new cells recognize the tissues and organs of the recipient’s body as foreign. 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, bone marrow transplant prognosis and long-term survival can vary greatly from person to person. Research and 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.