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Bone Marrow Transplantation (BMT) for Cancer Treatment

Bone marrow is a soft, sponge-like material found inside certain bones, such as the heads of the femur (thigh bone) and humerus (arm bone), the sternum (breast bone), and the hip bones. Healthy bone marrow makes red blood cells, white blood cells, and platelets. The marrow may be damaged by cancer or cancer treatments. The inability to make healthy cells can make a range of health problems. For example, weak red blood cells make it difficult to transport oxygen throughout the body, low white blood cells weaken the immune system, and low platelets can lead to excess bleeding.

Bone marrow transplantation (BMT) replaces damaged bone marrow with healthy bone marrow from a donor. It may need to be done with cancers, such as leukemia , lymphoma, and myeloma, or related conditions such as myelodysplastic syndromes.

  • How does bone marrow transplantation work?
  • What is bone marrow transplantation used for?
  • What are the types of bone marrow transplantation?
  • What does bone marrow transplantation involve?
  • What adverse effects can occur with bone marrow transplantation?

How Does Bone Marrow Transplantation Work?

Stem cells are predominately found in the bone marrow, but some occupy the bloodstream. These are called peripheral blood stem cells (PBSCs). If PBSCs are used in the transplant, it is referred to as peripheral blood stem cell transplantation (PBSCT). Umbilical cord blood also contains stem cells that can be used in stem cell transplantation.

When stem cells are transplanted, they enter the peripheral blood stream and travel to the bone marrow where they replace damaged stem cells and begin to make healthy blood cells. One advantage of using stem cells is that they can rapidly repopulate the full complement of blood and immune cells. Implanted stem cells find their own way to the bone marrow, as if they have a homing mechanism in place.

Stem cells can divide to form more stem cells or they can mature into blood cells.

What Is Bone Marrow Transplantation Used for?

BMT is used to sterilize the host bone marrow and replace it with health, noncancerous cells. Damage to stem cells can result from:

Chemotherapy and radiation therapy destroy rapidly dividing cells like cancer cells and healthy stem cells. A potentially fatal side effect to these treatments results in the destruction of stem cells (a condition called myelosuppression). BMT cannot be used as a preventive measure or reverse damage it if the bone marrow is completely destroyed.

Bone marrow damage can be caused by chemo- and/or radiation therapy that is:

  • Directed at the bone marrow—Most common in treatment of blood cancers like leukemias or lymphomas.
  • Not directed at the bone marrow—Other cancers are treated with systemic therapy that affects all cells in the body, including stem cells.

BMT and PBSCT are most frequently used in the treatment of the following cancers:

The roles of BMT and PBSCT are under investigation for the following cancers:

What Are the Types of Bone Marrow Transplantation?

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:

  • 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 3-year disease-free survival rates for autologous and allogeneic transplants. Disease-free survival means that you are living without any evidence that your disease or cancer has come back.

Estimated Survival Rates for Autologous Transplant
Disease 3-year Disease Free Survival
AML (1st complete remission)* 54%
AML (2nd complete remission) 73%
ALL (1st complete remission)** 91%
CML (1st chronic phase)** 93-96% (depending on donor relation)
Hodgkin's lymphoma (1st complete remission) 83%
Non-Hodgkin's lymphoma (1st complete remission) 72%

*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. **Data for first 100 days after transplant only.

Survival Rates for Allogeneic Transplant
Disease 3-year Disease Free Survival
AML (1st complete remission) 48%
AML (after 2nd complete remission) 48%
ALL (1st complete remission) 58%
ALL (2nd complete remission) 46%
CML (1st chronic phase) 57%
CML (Accelerated) 43%
CML (blastic)* 48%
Non-Hodgkin's lymphoma (1st complete remission)** 88%

*Data for 1 year after transplant only. **Data for first 100 days after transplant only.

What Does Bone Marrow Transplantation Involve?

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 1-2 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 4-5 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 4-5 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.

What Adverse Effects Can Occur With Bone Marrow Transplantation?

You may experience side effects associated with the transplant procedure. Most adverse events are caused by the conditioning regimen. The major complications associated with transplantation are:

  • Graft failure or rejection
  • Infection
  • Pneumonitis
  • Veno-occlusive disease
  • Graft-versus-host disease
  • Disease recurrence
  • Short-term side effects
  • Death
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. About half of all infections occur in the first 4-6 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 10-15% of systemic infection. Symptoms of a fungal infection include a dry, unproductive cough and change in breathing sounds. You may be given 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 20-50% 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, a dry, unproductive cough, and shortness of breath. Pneumonitis is managed with medication.

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 3 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 doctor for information and details specific to your treatment regimen.

Revision Information

  • Hematopoietic stem cell transplantation. Merck Professional Version website. Available at: http://www.merckmanuals.com/professional/immunology-allergic-disorders/transplantation/hematopoietic-stem-cell-transplantation. Updated April 2013. Accessed May 26, 2015.

  • Stem cell (bone marrow) transplant. Centers for Disease Control and Prevention website. Available at:http://www.cdc.gov/ncbddd/dba/stem.html. Updated February 20, 2015. Accessed May 26, 2015.

  • Stem cell transplant (peripheral blood, bone marrow, and cord transplants). American Cancer Society website. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003215-pdf.pdf. Accessed May 26, 2015.

  • US patient survival report. Health Resources and Services Administration Blood Cell Transplant website. Available at: http://bloodcell.transplant.hrsa.gov/research/transplant%5Fdata/us%5Ftx%5Fdata/survival%5Fdata/survival.aspx. Accessed May 26, 2015.