Bone marrow transplants are used to replace a patient’s damaged bone marrow with healthy marrow obtained from a donor. Bone marrow is the soft inner component of bones. It contains stem cells that produce red blood cells, white blood cells and platelets, as well as more developed precursors of these cells.

Healthy bone marrow is essential to the body’s ability to fight infections, prevent bleeding and carry oxygen to tissues. Bone marrow transplants may be performed in cancer patients to directly attack and kill cancer cells. However, they are most often used to restore bone marrow function that has been compromised by other cancer treatments, such as chemotherapy and radiation. Bone marrow transplants are not usually considered for a cancer patient unless there is evidence the patient will have a significant response to the other cancer treatments being contemplated.

The bone marrow used in a transplant procedure is sometimes obtained from patients themselves. In other cases, healthy marrow may be donated by an identical twin, another family member or someone unrelated to the patient.

Before the transplant, a surgical procedure is used to harvest stem cells from the donor’s bone marrow. The patient then receives the harvested stem cells through an intravenous (I.V.) line in a procedure similar to a blood transfusion. It takes between one to five hours to complete the transplant. 

Bone marrow transplants have varying degrees of success. Several factors – including shared race and ethnicity between the patient and the donor – can increase the odds of a successful transplant, and decrease the odds that the patient’s body will reject the new marrow.

The National Marrow Donor Program (NMDP) estimates that bone marrow or cord blood transplant could help more than 35,000 children and adults with life-threatening diseases every year. Patients who are diagnosed with leukemia, lymphoma and other blood cancers are responsible for approximately 85 percent of transplants facilitated by NMDP. There were more than 2,600 marrow and cord blood transplants in 2005, according to the NMDP.

Advances in transplant procedures have made transplants a viable option for more patients. Research continues to develop transplants that are less dangerous and more effective for a wider range of people and conditions.

Bone marrow transplants help patients replace damaged bone marrow with healthy donor marrow. The bone marrow contains stem cells that grow into red blood cells, white blood cells and platelets.

The vast majority of bone marrow transplants are performed to treat cancer patients whose marrow has been damaged by chemotherapy or radiation treatments. Transplants are also performed to replace defective bone marrow in patients without cancer.  

Bone marrow is the soft and spongy material found inside a person’s bones. Hematopoietic (blood-forming) stem cells are found in the marrow. These cells divide and form any one of the following:

• Additional hematopoietic stem cells. These cells can then produce additional cells of any type.
  
  
• White blood cells. Protect the body from diseases, including potentially life-threatening infections.
  
  
• Red blood cells. Carry oxygen to all parts of the body and take carbon dioxide from the cells back to the lungs to be expelled from the body.
  
  
• Platelets. Help clot blood to prevent excessive bleeding or bruising.

While most of the body’s hematopoietic cells are found in bone marrow, some appear in the bloodstream. These are called peripheral blood stem cells (PBSCs). In addition, blood in the umbilical cord contains hematopoietic cells. All of these sources of stem cells can be used in bone marrow transplants.

Bone marrow transplants are performed in cancer patients for two main reasons:

• To directly attack and kill cancer cells. Transplanted bone marrow can recognize cancer cells that exist in a patient as being abnormal, and will attack and try to destroy the cancer cells.
  
  
• To support other cancer-fighting therapies. High doses of chemotherapy or radiation therapy are often used to target and kill cancer cells. However, these treatments have the undesirable side effect of killing normal cells as well. Bone marrow cells generally are more vulnerable to these destructive effects than any other cells in the body.

Bone marrow transplants can help replace these destroyed cells that are essential to life. As a result, physicians are able to administer higher doses of chemotherapy and radiation to a patient with the knowledge that destroyed healthy cells can be replaced with a bone marrow transplant. Higher doses of these anticancer treatments increase the odds of successfully eradicating the cancer. Bone marrow transplants are not usually considered for a cancer patient unless there is evidence the patient will have a significant response to the other cancer treatments.

A transplant provides patient's bone marrow with new stem cells that can develop into cells designed to fight infections, prevent bleeding and carry oxygen to tissues. Hematopoietic cells from any source – bone marrow, bloodstream or umbilical cord – can be used in bone marrow transplantation. There are three types of transplants:

• Autologous transplant. A patient’s own stem cells are used.
  
  
• Syngeneic transplant. Stem cells from an identical twin are used. Because identical twins share the same genes, there is no risk of rejection in this form of transplant.
  
  
• Allogeneic transplant. Stem cells come from someone other than the patient or an identical twin. This can be a family member, or someone unrelated to the patient.

Bone marrow transplants are most often used in treatment of leukemia or lymphoma, and are most effective when these diseases are in remission. Other cancers that may require bone marrow transplants include neuroblastoma and multiple myeloma. Researchers also are evaluating the potential effectiveness of using bone marrow transplants in the treatment of a host of other cancers, as well as to reduce the risk of rejection following organ transplantation.

A group of specialists, known as the transplant team, are typically involved with all aspects of the bone marrow transplant. The team may include:

• Physicians who specialize in oncology, hematology, bone marrow transplants and infectious diseases
• Transplant nurses
• Dieticians
• Physical therapists
• Social workers

Initially, patients will be evaluated to determine if they are good candidates for providing their own bone marrow cells or blood stem cells for transplant. If the bone marrow is extensively affected by cancer, transplant probably will not be an option. If the patient does not have an identical twin, an allogeneic transplant (cells from someone other than the patient or an identical twin) will be the only option. 

Those who are receiving stem cells from an allogeneic donor will have to be matched to an individual whose stem cells closely resemble their own. In looking for such a match, a set of proteins called human leukocyte-associated (HLA) antigens will be examined. These proteins are found on the surface of the cell and are identified through a blood test.

In general, the more HLA antigens that match between donor and patient, the greater the likelihood that the patient’s body will accept the new stem cells. A higher degree of match makes it less likely that the patient will develop graft-versus-host disease (GVHD) This is a complication that occurs when a donor’s white blood cells perceive the patient’s normal cells as foreign and attack them.  

When matching a patient to a donor other than an identical twin, a family member is the first choice, with brothers and sisters usually providing the best match. However, only 25 percent to 35 percent of patients have siblings who are an HLA match, according to the National Cancer Institute (NCI). A parent may not be considered an acceptable match because the patient will have HLA material from each parent.

If a suitable match is not found inside the family, the patient may need to contact a nationwide donor registry list maintained by the National Marrow Donor Program. According to the NCI, the likelihood of obtaining HLA-matched stem cells from an unrelated donor is approximately 50 percent. These odds improve significantly between individuals who share the same ethnic and racial background. However, many racial groups are underrepresented in the nationwide donor registry, making it even more difficult to find matches for patients who are African American or Asian.

In addition, because of the complexity and diversity of HLA antigens, it is extremely difficult to match patients to donors who are unrelated if the patient has uncommon or rare HLA antigens.

In some cases, stem cells will be obtained from umbilical cord blood. This can only take place when a pregnant woman makes arrangements with a cord blood bank before her baby’s birth. Public cord blood banks accept donations of umbilical cord blood that may be used in patients waiting for a match. Private cord blood banks store umbilical cord blood for a fee. These stem cells can be used in the child or another family member should the need arise in the future.

Families will most often consider storing umbilical cord blood privately when they have a child or close relative with a medical condition for which bone marrow transplants may be performed.  A family history of these conditions often is enough for parents to consider this option. Conditions treated with bone marrow transplants include:

• Leukemia
  
  
• Lymphoma
  
  
• Aplastic anemia (condition that prevents blood cell formation)
  
  
• Sickle cell anemia (genetic chronic anemia marked by sickle-shaped red blood cells)
  
  
• Severe combined immune deficiency (group of inherited disorders characterized by a lack of immune response)

Finally, stem cells also can be obtained from the bloodstream itself. This is often the source for autologous transplants (stem cells obtained from the patient), and it is also being used in an increasing number of allogeneic transplants.

Stem cells obtained from the patient must be largely free of cancer. After the cells have been harvested, they can be treated in a procedure known as “purging,” which removes any cancer cells from the harvested cells. This process helps minimize the chances of cancer returning after the transplant. The purging process also damages some healthy stem cells, so more cells are harvested before an autologous transplant than in other transplants to ensure an adequate supply of healthy cells.

Before a transplant can occur, donor stem cells must be harvested. Either a general anesthetic (which puts the patient to sleep) or a regional anesthetic (which numbs all feeling below the waist) will be administered to the donor.

The stem cells to be used for transplant will be harvested from the bone marrow, the soft center of the bone. To obtain these cells, a needle is inserted through the skin and into the hip bone. In rare cases, the needle may be inserted into the breastbone to obtain the cells.

A sample of marrow containing the stem cells is then drawn out of the bone. This process takes about an hour, and involves between 100 and 200 needle punctures to remove 500 to 1,000 cubic centimeters (1 to 2 pints) of marrow. After the marrow has been harvested, it is processed to remove all blood and bone fragments.

In the donor, the area from which the bone marrow is taken may be stiff or sore for a few days. In addition, the donor may feel tired. Most donor patients are back to normal within two to three days, though other patients may take up to a month for full recovery.

In an allogeneic transplant, marrow received from a donor who has the same red blood cell type (e.g., A, B, C)as the patient will immediately be intravenously transplanted. However, if the red blood cell types do not match, the red cells will first have to be separated and discarded.

In an autologous transplant, the cells are stored until after the patient is finished with chemotherapy or radiation therapy. The harvested bone marrow can be combined with a preservative and frozen in a technique called cryopreservation. This keeps the stem cells alive until they are needed, and allows the cells to be stored for many years. This technique may be used by patients who plan to use their own stem cells for later transplant (such as after completion of chemotherapy or radiation therapy).

When harvesting umbilical cord stem cells, blood is obtained from the umbilical cord and placenta after the birth process is complete. If the mother consents, the umbilical cord is processed and frozen for storage by a cord blood bank. Collected stem cells are typically used only in children or small adults, as it is possible to retrieve only a limited amount of blood from the umbilical cord and placenta.

Patients who are to receive donated stem cells will first undergo a course of high-dose anticancer medications or radiation treatment. These treatments are critical for the patient and may have significant risks and side effects. When these treatments are completed, the stem cells will be given to the patient.

The patient will receive the stem cells through an intravenous (I.V.) line in a procedure similar to a blood transfusion. It takes between one to five hours to complete the transplantation. Once in the body, the cells form and mature to restore the patient’s blood cells.

Immediately after the transplant, patients usually remain in the hospital under close supervision. Patients are closely monitored until testing reveals adequate levels of white blood cells and platelets. Once the transplanted cells enter the patient’s bloodstream, they travel to the marrow and begin to produce new white blood cells, red blood cells and platelets. This process is known as engraftment, and it usually occurs two to four weeks after the transplant procedure. A physician can detect engraftment by regularly checking blood counts. Patients will also be monitored to ensure that:

• New bone marrow is functioning properly
• There are no signs of serious graft-versus-host disease
• The cancer has been controlled

Following a bone marrow transplant, it takes longer for a patient to experience complete recovery of immune function, which is the production and action of cells in fighting disease. Patients who receive an autologous transplant may need several months for this process to develop. Those patients who undergo allogeneic or syngeneic transplants may wait one to two years before experiencing full recovery of immune function.

After some allogeneic bone marrow transplants, such as for treating certain leukemias, a process known as the graft-versus-tumor (GVT) effect must occur for success.  The GVT effect develops when white blood cells from the donor recognize cancer cells remaining in the patient’s body and begin to attack them.

Physicians can use various blood tests to be sure that new blood cells are being produced and that the cancer has not returned. They also may use a needle to remove a small sample of bone marrow for examination under a microscope.  This is known as a bone marrow aspiration and it helps reveal how well the new bone marrow is working in the patient.  

Bone marrow transplants have varying degrees of success, particularly when the donor is someone other than the patient or an identical twin (allogeneic transplantation). This type of transplantation is more likely to be effective in younger people.  After the age of 30, vulnerability to graft-versus-host disease (GVHD) rises rapidly, especially in those between the ages of 40 and 55.

When effective, bone marrow transplants can help treat a number of cancers, including:

• Acute leukemia. Younger patients tend to fare better than older patients, although there are success stories in all age groups. Patients with acute leukemia who have relapsed after trying other treatments usually find a bone marrow transplant to be their best option for successful treatment.
  
  
• Chronic granulocytic leukemia. Bone marrow transplants are often used for patients who have this disease and have a human leukocyte-associated (HLA)-matched brother or sister.
  
  
• Non-Hodgkin’s lymphoma. Patients with these types of tumors are among the best candidates for a combination of high-dose chemotherapy or radiation combined with a bone marrow transplant. They include two subsets:
  
  
• • Aggressive non-Hodgkin’s lymphomas. While these diseases may be successfully treated with other therapies, bone marrow transplants are often the most effective for any later relapse of these diseases.
    
    
  • Low-grade non-Hodgkin’s lymphomas. Allogeneic transplants have increasingly been used to treat this disease, with a large proportion of patients reportedly responding well to the treatment.
    
    
• Hodgkin’s lymphoma. Patients usually do well using standard therapies to treat this disease. However, patients who do relapse often have poor success with standard therapy and appear to benefit from bone marrow transplants.
  
  
• Other blood cancers. Patients with hairy cell leukemia and chronic lymphocytic leukemia (CLL) have shown excellent responses to bone marrow transplants. Transplants also have been used to benefit some patients with multiple myeloma.
  
  
• Solid tumors. Transplants have been used successfully  to treat a wide variety of carcinomas and sarcomas. However, some solid tumors – including lung cancers, breast cancers, ovarian cancer and gastrointestinal cancers – are not sensitive enough to high-dose chemotherapy and radiation to make transplants a standard of treatment.
  
  Solid tumors in children, particularly neuroblastomas, also can sometimes be effectively treated using bone marrow transplants.

A bone marrow transplant is a potentially dangerous procedure that is not to be undertaken lightly. Bone marrow transplants are most effective when they occur early in the course of a patient’s disease.  At this point, the patient has less cancer and the disease has not had a chance to become resistant to therapy. However, the significant risks that come with bone marrow transplants make physicians less comfortable about mandating this treatment so early in the disease when other, less invasive treatments might be equally effective.

For this reason, many physicians will first try the less potentially harmful treatments and closely monitor them for progress. If the treatment appears to be largely ineffective, bone marrow transplant may become a viable alternative. 

Patients who undergo bone marrow transplants should be aware that there is always a significant chance that the body will reject the transplanted bone marrow, with potentially life-threatening consequences. Infections and graft-versus-host disease can be fatal for patients who have recently undergone a bone marrow transplant. The risks associated with bone marrow transplants must be weighed against the potential life-saving benefits of the procedures. Risks for donors are minimal, while patients who receive the transplantation face a greater number of potential complications.

Transplant patients

Patients who undergo a bone marrow transplant may experience an increased susceptibility to bleeding and infection, especially in the first month after the procedure. As a result, a physician may prescribe antibiotics to prevent infection and order transfusions of platelets to prevent bleeding and red blood cells to treat anemia.

Other short-term side effects of bone marrow transplants include:

• Nausea and vomiting
• Fatigue
• Loss of appetite
• Mouth sores
• Hair loss
• Skin reactions

Long-term risks associated with transplants are largely a result of chemotherapy or radiation therapy administered prior to the transplant. These include:

• Infertility
• Cataracts (clouding of the eye lens)
• Secondary cancers
• Liver, kidney, lung or heart damage

In some cases, the body will reject the new marrow. This complication is more likely in patients receiving an allogeneic transplant for aplastic anemia. In some cases, a second transplant may be necessary.

Patients who receive allogeneic transplants may experience a complication known as graft-versus-host disease (GVHD). This occurs when a donor’s white blood cells identify normal cells in the patient’s body as foreign and attack them.  Damage to the skin, liver, intestines and other organs may result. GVHD can take two forms:

• Acute GVHD. Occurs within a few weeks of the transplant. It usually doesn’t last long but in severe cases, it can be fatal.
  
  
  
• Chronic GVHD. Develops much later than the acute form of the disease and is often difficult to treat. However, patients who experience this disorder after an allogeneic transplant for leukemia are less likely to have recurrent leukemia.

To prevent GVHD, patients may receive medications that suppress the immune system known as immunosuppressants. Donated stem cells can also be treated with a process called T-cell depletion that removes the white blood cells that cause GVHD. If GVHD has already developed, it can be treated with steroid medications or immunosuppressive agents.

Bone marrow donors

Bone marrow donors usually do not experience any significant problems after the procedure. Only a small amount of marrow is actually removed, and the most common side effect is some stiffness and soreness at the donation site for a few days following the procedure. Some people also may feel tired for a short time after donating. The only significant risks are those associated with any surgical procedure, such as a reaction to anesthesia or medical complications.

The donor’s body replaces the lost bone marrow within a few weeks of donation. Total recovery time varies from a few days to a several weeks.

Bone marrow transplant is a fast-changing field, with new advances occurring regularly. At present, two new types of bone marrow transplants are being studied in clinical trials and producing significant results. They are:

• Mini-transplant. Also called a non-myeloablative or reduced-intensity transplant, this is a type of allogeneic transplant that uses lower, less toxic doses of chemotherapy or radiation to prepare patients for bone marrow transplants. These lower doses do not completely destroy the patient’s bone marrow but still reduce levels of cancer cells and suppress the immune system to prevent rejection of the transplant. These treatments are being used in older patients and those with solid tumors. The number of transplants performed in patients older than 50 years has increased steadily since 1984.
  
  Unlike a traditional bone marrow transplant, cells from both the donor and the patient coexist in the body for a while after a mini–transplant. However, as the donor cells begin the process of engraftment, they may trigger the graft-versus-tumor (GVT) effect and begin destryoing cancer cells that remain after chemotherapy or radiation.
  
  Mini-transplants are being tested for use in treating:
• • Leukemia
  • Lymphoma
  • Multiple myeloma
  • Other cancers of the blood
    
    
• Tandem transplant. A type of autologous transplant that involves two sequential courses of high-dose chemotherapy with a stem cell transplant. In most cases, two treatment courses are given several weeks to several months apart.
  
  Researchers are hopeful this method will help prevent cancers from recurring later. It is being tested for use in patients with multiple myeloma.

Research also has focused on optimal timing for transplants in cancer patients, better management of transplant complications and improved methods for matching donors and patients. Medications, including vaccines, continue to be studied to prevent infections and graft-versus-host disease, which can be life-threatening. Researchers are also examining factors, such as proteins or specific stem cells, that may help predict the success of a transplant. Other areas of research are investigating other uses for bone marrow transplants, such as following an organ transplant to reduce the risk of rejection. There are numerous clinical trials being conducted in the areas of bone marrow, stem cell and cord blood transplants. A patient’s physicians can best determine if an individual is a candidate for a clinical trial.

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about bone marrow transplants:

1. Is a bone marrow transplant a treatment option for me?
   
   
2. What other treatments may be tried before the transplant?
   
   
3. Can I donate my own bone marrow?
   
   
4. If not, how will a matching donor be located?
   
   
5. What type of tests will be needed to determine compatibility?
   
   
6. What are the chances that I will reject the transplanted cells?
   
   
7. How often can I receive a bone marrow transplant for my cancer?
   
   
8. How can you determine if the bone marrow treatment has been successful?
   
   
9. What is my prognosis if I receive a bone marrow transplant?
   
   
10. Am I at greater risk for other conditions after I have received or given a bone marrow transplant?
    
    
11. What type of treatments might I need after the bone marrow transplant?
    
    
12. If I am a donor, how often can I donate my bone marrow?
    
    
13. Should I consider storing stem cells for future transplants?
    
    
14. What are the greatest risks associated with bone marrow transplants?
    
    
15. Am I a candidate for any clinical trial?