Bone Marrow Transplantation (BMT) for Cancer Treatment

Autologous Transplant

In an autologous transplant, stem cells from your own peripheral blood or bone marrow are collected (harvested). They are placed in frozen storage (cryopreserved) prior to treatment of the cancer with high-dose chemotherapy. Once chemotherapy treatment is complete, the stem cells are reinfused (put back into your body). The stem cells will restore the bone marrow. The new blood marrow can restore production of red and white blood cells and platelets.

Prior to reinfusion, healthy stem cells are separated from any cancer cells that may be present in the harvested bone marrow. This is done to avoid reintroducing cancer cells into the bone marrow. However, it has never been shown that this filtering process is either required or effective.

Allogeneic Transplant

In an allogeneic transplant, you receive someone else's stem cells. The donor's tissue type (which is different than blood type) must closely match yours. There are several types of allogeneic transplants, including the following:

• Syngeneic—The donor is your identical twin.
• Related—The donor is related to you, usually your sibling.
• Unrelated—The donor is no relation to you.

Only an identical twin has the same exact tissue type as your own. Any other sibling with the same biological mother and father has a 25% chance of matching your tissue type. If no one in your family is a match, your doctor can search for a donor in the National Marrow Donor Program's Registry of 4.5 million adult volunteer donors and 15,000 umbilical cord blood units.

Survival Rates

The following tables list approximate 5-year disease-free survival rates for autologous and allogeneic transplants. Disease-free survival means that you are alive without any evidence that your disease or cancer has come back.

*Complete remission (CR) is a decrease in tumor burden by several orders of magnitude. In addition, bone marrow examinations and peripheral blood counts are normal and there is no detectable leukemia elsewhere in the body.

Source: Otto SE. Oncology Nursing ; 2001.

Obtaining Bone Marrow

Whether the transplant is allogeneic or autologous, the procedure for harvesting the bone marrow is similar. The donor (which can be you or someone else) is given local anesthesia. Several small cuts are made in the skin over the area where the marrow will be removed (for example, the hip). A large needle is inserted through the cuts and into the center of the bone to withdraw the bone marrow. This process takes about one to two hours.

The harvested bone marrow is processed to remove blood and bone fragments. If the transplant is autologous, usable stem cells must be separated from any residual cancer cells. In the past, the harvested cells were mixed with chemotherapeutic agents or monoclonal antibodies. Since this purging process tended to remove some healthy stem cells along with the cancer cells, it is currently being replaced with other techniques that identify wanted cells, separate them out, and discard the cancer cells.

For an autologous transplant, the marrow may be immediately transfused back into you or cryopreserved (frozen) for many years. For an allogeneic transplant, the marrow is mixed with the preservative DMSO and cryopreserved until it is transplanted.

Obtaining Peripheral Blood Stem Cells

A process called apheresis or leukopheresis is used to obtain peripheral blood stem cells for transplant. For four to five days before the procedure, the donor (which can be you or someone else) may be given medication to increase the number of stem cells released into the blood stream.

During apheresis, a catheter is placed in a large vein in the neck or chest area or a needle is placed into a large vein in the arm. Blood is removed and sent through a machine that removes the stem cells. The blood is returned to the donor and the collected stem cells are stored. Apheresis takes about four to five hours. The collected cells, which may require treatment to remove unwanted cells, are frozen until they are transplanted.

Peripheral blood stem cell collection is now the preferred method of harvesting stem cells for transplant.

Transplanting the Stem Cells

Details of the transplantation procedure vary with the cancer being treated. To prepare your body to receive the transplant, a conditioning regimen is generally required prior to any transplant. This involves the use of radiation therapy and/or high-dose chemotherapy in order to destroy the original cancer and create space in the marrow cavity for the transplanted stem cells to grow and replicate.

After the conditioning regimen, you will receive the stem cells through a central venous catheter, which is usually placed in the chest or neck. This part of the procedure is called the rescue process.

Graft Failure

Graft failure or rejection is the failure of marrow recovery to return or the loss of marrow function after the initial period of recovery. It is a relatively rare occurrence, with an incidence of 5% to 15%. If this occurs, your doctor may consider retransplantation.

Infection

Infection is the most common side effect of transplantation. Fifty percent of all infections occur in the first four to six weeks following transplantation. Usually, it is bacteria from your skin or gastrointestinal tract that leads to infection. Fever is the main symptom.

Fungal infections occur, but are far less common and account for about 10% to 15% of systemic infection. Symptoms of a fungal infection include a dry, unproductive cough and change in breathing sounds. You may be given fluconazole (an antifungal agent) to prevent infection.

Viral infections can occur too. Herpes simplex virus]]> (HSV), which lies dormant in many people, may be reactivated. Other viruses associated with transplantation include ]]>cytomegalovirus]]> and varicella-zoster virus. You may be given antiviral medication to help prevent or treat these infections.

To help prevent infection, your healthcare team will likely do the following:

• Maintain a protective environment
• Help you maintain good hygiene
• Frequently monitor your vital signs and perform complete examinations

Pneumonitis

Interstitial pneumonitis accounts for 40% of transplant deaths. This type of pneumonia usually occurs within the first 100 days of the transplant. Bacterial infections account for 20% to 50% of cases. The most common viral cause is cytomegalovirus. Risk factors for developing interstitial pneumonitis include the following:

• Use of immunosuppressant drugs.
• Lung damage, which can result from the radiation used in the conditioning regimen.
• Total body irradiation.
• Presence of opportunistic infections—These are infections that take advantage of the fact that the body's normal defenses are compromised. Normally, your immune system would be able to fight these infections.

Symptoms include fever; dry, unproductive cough; and shortness of breath. Pneumonitis is managed with medications.

Veno-occlusive Disease (VOD)

Veno-occlusive disease (VOD) is a complication of the conditioning regimen for BMT. It occurs in about 20% of people undergoing allogeneic BMT and 10% of people undergoing autologous BMT. In VOD, there is occlusion (complete blockage) of the central veins of the liver, which results in venous congestion and damage to the liver cells. Symptoms include weight gain, enlarged liver, pain in the upper abdomen, high blood bilirubin levels, and ascites (fluid accumulation in the spaces between the tissues and organs in the abdomen).

Graft-versus-Host Disease (GVHD)

Graft-versus-host disease, an immune-mediated reaction, can occur after an allogeneic transplant. The white blood cells in the donor marrow identify your cells as foreign and attack them. This condition is usually treated with steroids or other immunosuppressive agents.

GVHD is divided into acute and chronic:

• Acute—This occurs within 100 days of transplant. Target organs are the skin, the gastrointestinal tract, and the liver.
• Chronic—This typically occurs more than 100 days after transplant. Almost every organ can be affected by chronic GVHD.

Cancer Recurrence

Cancer recurrence (relapse) is the most significant problem after BMT. Relapse is more common after an autologous transplant. This may be due to "hidden" malignant cells in the transplanted stem cells. Disease recurrence is the major factor related to long-term mortality, which means death more than three months after transplant.

Short-Term Side Effects

Some short-term side effects that you may experience while undergoing this procedure include nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions. Additional side effects may occur. Talk with your healthcare provider for information and details specific to your treatment regimen.