February 20, 2007

Occasionally, Cancer.Net asks a member of the American Society of Clinical Oncology (ASCO) to write an article on his or her area of expertise. This four-part series is written by Edward Agura, MD, an advisory panel member for the Cancer.Net Editorial Board. Dr. Agura is Director of the Program in Blood and Marrow Transplant at Baylor University Medical Center in Dallas, Texas.

This is the first in a four-part series of articles on bone marrow and stem cell transplantation. The series will prepare you to ask your transplant team meaningful questions and help you to understand the answers. The series will also walk you through the goals of bone marrow transplantation, the types of transplantation donors and what to expect as a donor, side effects, questions to ask your transplant team, and a transplant timeline. This article provides an overview of bone marrow and stem cell transplantation and explains the differences between autologous and allogeneic transplants.

Blood and marrow transplantation is a medical (not a surgical) procedure, lasting weeks to months from start to finish, in which diseased marrow (a spongy, fatty tissue found on the inside of larger bones) or immune system is replaced by a healthier one. For people with cancer, the goal is to destroy every last cancer cell. For people with genetic diseases, the goal is correction of the underlying genetic disease.

To accomplish these goals, the bone marrow must be replaced and/or treated. And in order to accomplish that goal, the doctor will first collect stem cells that will replace the destroyed tissue.

People stay alive by a process of continual self-renewal. Wounds heal, hair grows, and internal organs renew themselves. If this process did not occur, people would not live very long. Rare and highly specialized cells called stem cells distributed throughout the body are responsible for this renewal process.

Every part of the body has its own population of stem cells, which help to renew the organ in which they live. For example, stem cells found in the skin help to renew the skin when it is injured, and liver stem cells help to renew the liver. Blood and bone marrow stem cells help renew the blood and bone marrow.

The natural home of blood and marrow stem cells is inside the bones—in the marrow cavity itself. From this location, they perform their crucial function: to multiply and produce their unique offspring: red cells (also called erythrocytes), white cells (also called leukocytes), and platelets. These are the cellular components of the human bloodstream. Red blood cells are responsible for bringing oxygen to the body's organs and tissues and carrying away waste from the body's organs and tissues. White blood cells are responsible for helping to protect the body from infection. Platelets are responsible for causing blood to clot, which helps to control bleeding. Within this unique "family," blood/marrow stem cells are the parents, and white cells, red blood cells, and platelets are the children.

During the process of bone marrow transplantation, stem cells from the marrow are first removed and then later put into the patient's body. The replacement stem cells may come from the patient, or may come from a donor (another person). The choice of which to use depends on many factors, including the type of illness being treated and the health of the patient's own marrow. When the patient receives his or her own stem cells, it is called an autologous transplant; when donor cells are used, it is called an allogeneic transplant.

Before the patient receives the replacement stem cells, he or she will be treated with chemotherapy and/or radiation therapy, typically for five to seven days, to destroy the diseased bone marrow. Then, the replacement stem cells are transferred into the patient's bloodstream through a simple, intravenous (IV) transfusion. No surgery is involved. The new stem cells float through the bloodstream and gradually find their way back "home" to the bone marrow space. Once in the marrow space, the stem cells "plant" themselves and begin to grow.

It is important to note there is a difference between bone marrow stem cells and embryonic stem cells. Embryonic stem cells are derived from human embryos and are not currently used for bone marrow transplantation.

The goals of blood and marrow transplantation

Patients seek to be cured. Transplantation is a powerful method that has the capability of curing cancers and some genetic diseases which involve the blood. A list of diseases commonly treated this way, along with the preferred transplant method, is below.

The differences between AUTO and ALLO transplants

An autologous transplant, known as an AUTO, uses a patient's own stem cells. The stem cells are removed and stored first (days to weeks ahead), then the patient is given chemotherapy and/or radiation therapy for about one week. At the end of the treatment, the frozen stem cells are thawed and given back to the patient as an intravenous transfusion, often through a vein in the arm.

An allogeneic transplant, known as an ALLO, uses a donor who is genetically matched with the patient for a factor known as "tissue type." The patient's siblings usually have the best chance of being a complete match. Other family members occasionally can match. Or, a volunteer donor may be the best match for the tissue type. During an ALLO transplant, the patient first undergoes treatment very similar to that given during an AUTO transplant (described above). However, the timing of stem cell donation is coordinated, so it occurs at the same time as the end of the chemotherapy and/or radiation therapy the patient receives. Donor stem cells are collected on or near the actual transplant day, and the patient receives these fresh and unfrozen, as an intravenous infusion.

Both AUTO and ALLO transplants kill cancer with dose intensity (high doses of chemotherapy and/or radiation therapy). With AUTO transplants, the cancer-killing effect ends when the chemotherapy/radiation therapy ends. (The remainder of the treatment course is simply to help patients recover from side effects.) In distinction, the ALLO transplant continues to battle cancer even after the chemotherapy/radiation therapy are done.

ALLO transplants have two advantages that make them superior to AUTO transplants for eliminating cancer. The first has to do with giving the patient a cancer-free stem cell product. With an AUTO transplant, there is always the inherent risk that cancer cells will be contained in the frozen stem cell product. The risk does not exist if the stem cells come from a healthy donor. The second reason has to do with the new immune system that develops after an ALLO transplant. This new immune system has an ability to attack cancer cells that may have escaped the chemotherapy/radiation therapy given at the beginning of the transplant process. This enhanced effect is especially strong with certain kinds of cancers and is given the name, graft versus tumor (GVT) effect. On the other hand, a patient receiving an ALLO transplant faces tissue rejection risks that an AUTO transplant patient does not.

Choosing the type of transplant

There are many medical factors involved in the decision regarding which stem cell source to use. Some of the most important ones include whether the bone marrow contains cancerous cells, the extent of bone marrow injury caused by previous chemotherapy, the disease type itself, and the health and age of the patient.

The decision is complex; it cannot be made without the input of a doctor who specializes in transplant medicine and has performed an in-person evaluation of the patient and the potential donor. This means the patient may need to travel to a center where transplantation is routinely practiced to have a consultation.

At the consultation, other nonmedical factors are also considered, such as the patient's support system, their ability to take time away from work or family, insurance coverage, and access to transportation.

When the disease type irreversibly involves the bone marrow, an allogeneic (donor-type) transplant is the only type of transplant that offers a chance to cure. Fortunately, at least one out of three patients turns out to have a suitably matched brother or sister who can donate. The tissue typing is done through a blood test of the potential donor. Transplant can then move forward rapidly.

Unrelated and cord blood donors

If siblings do not match, other family members may be tested, but such matches occur only occasionally. However, people who need a donor can turn to the volunteer and cord blood registries.

Formed in the mid-1980s, volunteer registries are now very large (7 million volunteer donors worldwide). At least two-thirds of patients who need a donor can find one through these registries.

And, for people who cannot find a living matched donor, there is hope with the ever-expanding umbilical cord blood registries. While still a relatively young and emerging source of stem cells, cord blood units are used at cancer centers around the world. The results in children have been excellent. In adults, the technology is still underdeveloped, and patients may face additional risks that should be discussed with the doctor. Read more about Donating Umbilical Cord Blood.

Duration of bone marrow transplantation

The duration and timing of bone marrow transplantation is often misunderstood. Many patients think of it as a surgery, which it is not. Many more are surprised when they are told that blood and marrow transplantation does not happen suddenly. Instead, transplantation is a process that takes weeks and months from beginning to end.

Questions to ask your transplant team regarding timing:

• How long will I be away from home?
• When will I feel strong enough to return to full-time work?
• When will I start to feel better than I feel today?

What to expect as the donor

Being a stem cell donor has changed greatly in recent years. Today, most donors undergo a peripheral blood stem cell (PBSC) collection rather than a bone marrow harvest procedure (an operation that involves going to the hospital for a day surgery, undergoing general anesthesia [medication that puts you in a deep sleep], and having one or two transplant surgeons extract marrow from the hip bones using needles). For five days leading up to the PBSC procedure, donors receive injections (lasting 5 minutes a day) of a white blood cell growth hormone called G-CSF (Neupogen). On the fifth day, a needle is placed in each arm and blood is circulated through a machine, which collects the stem cells and returns the unused portion of the blood back to the donor. This takes about three hours and may be repeated on a second donation day. There is very little blood loss. Side effects with this type of procedure may include headaches, bone soreness, and the discomfort of needles during the process.

Occasionally, donor cells do not grow. The chance of this happening depends on many factors, the most important being whether the patient has had previous chemotherapy (prior chemotherapy may indicate success), the intensity (strength) of the transplant treatment to destroy the original bone marrow (stronger may indicate growth), and the amount of donor cells provided (more is better). In most cases, the solution is to obtain more cells from the donor. Most second donations result in the successful growth of donor cells.

Additional Resources

National Marrow Donor Program

Blood and Marrow Transplant Information Network

Bone Marrow and Cord Blood Donation and Transplantation from the U.S. Department of Health and Human Services

National Bone Marrow Transplant Link

The Leukemia and Lymphoma Society

More Information

Part II: Bone Marrow and Stem Cell Transplantation: Special types of transplantation

Part III: Side Effects of Bone Marrow and Stem Cell Transplantation

Part IV: Questions and Answers About Bone Marrow and Stem Cell Transplantation

Donating Bone Marrow

Finding a Treatment Facility