Allogeneic stem cell transplantation for young adults

Allogeneic stem cell transplantation (SCT) involves the use of stem cells from someone other than you. The donated stem cells can come from a relative or someone not related to you.

Before beginning an allogenic SCT, you will receive a conditioning treatment that consists of either chemotherapy or radiation. Some people receive both. Conditioning treatment is given to destroy any remaining cancer cells in the body. It weakens your own immune system so that your donor's cells are not rejected.

Conditioning treatment allows the new cells to move through your bloodstream to your bone marrow, where the donor cells begin to grow and produce new blood cells, including red blood cells, white blood cells, and platelets. This process is called “engraftment.” 

For some types of blood cancers, an allogeneic SCT may work directly to destroy cancer cells. This is called the graft-versus-tumor (GVT) effect. The GVT effect happens when white blood cells from the donor (the “graft”) identify any remaining cancer cells (the “tumor”) in the patient as foreign and attack them. For some people, GVT is crucial for the effectiveness of their treatment. It can help prevent the cancer from coming back. This benefit can only occur in allogeneic SCT; it does not occur in an autologous SCT.

Tissue typing for allogeneic transplantation

Once it is determined that allogeneic SCT is a treatment option for you, your doctor will begin to search for a suitable donor. A close match is important because it improves your chances for a successful transplant by helping the donor stem cells engraft (grow and make new blood cells in your body) and reducing the risks of complications.

HLA matching: People have different sets of proteins or markers called human leukocyte antigens (HLAs) on the surface of most of their cells. They make up a person’s tissue type, which varies from person to person. Blood tests of both the patient and potential donor are done to determine if there is an HLA match. 

There are many HLA markers. Individuals inherit half of their HLA markers from their mothers and half from their fathers, so most often the ideal donor is your sibling (who has inherited the same HLA markers). On average, a person has one chance in four of having the same HLA type as their sibling, but many people do not have a sibling with the same tissue type. For those who do not have a matched family donor, an unrelated donor may be found through a volunteer donor registry. 

Mismatched unrelated donor transplantation: Your doctor will try to match 10 to 12 HLA markers to lower the risk of graft-versus-host disease (see below). In recent years, advances in medicine have allowed for the use of stem cell donors who are mismatched, meaning that not all 10 or 12 markers are a perfect match. Use of medications following transplant allows for mismatched donors while still lowering the risk of graft-versus-host disease.

Haploidentical transplantation: To increase the number of potential donors, some transplant centers have begun to perform half-match (haploidentical) transplants for those who cannot find a closely-matched HLA donor.

In many cases, a healthy, first-degree relative (a parent, sibling, or child) can be a half-match donor and donate stem cells. Because a child receives half of their HLA markers from a parent, a biological child and their parent will always be a half match, while there is only a 50 percent chance of a sibling being a half match. As a result, most individuals will have a suitable related haploidentical donor.

Cord blood transplantation: Cord blood is blood taken from the umbilical cords of newborn babies. Cord blood may be an option for people without a well-matched donor. Unfortunately, cord blood units tend to contain fewer stem cells and may be difficult to use in people with larger body sizes. Cord blood transplant patients also have an increased risk of graft failure. However, cord blood is available much more quickly (potentially within two to four weeks), while it may take a month or more to obtain matched unrelated donor grafts. Another advantage of cord blood transplants is that cord blood may require a lower level of HLA matching between the donor and recipient.

Possible complications

One complication of allogeneic transplantation is that your body—despite the treatment to suppress the immune system—may reject the donated stem cells before they are able to engraft in the bone marrow. Your immune cells may see the donor’s cells as foreign and destroy them.

Graft-versus-host disease (GVHD) is a common but potentially serious complication of SCT. Sometimes, the cells from the donor (graft) sense that healthy cells of the patient (host) are foreign and attack and damage the patient’s normal cells. GVHD can be mild, moderate, or severe. In some cases, it can be life threatening.

A close HLA match between the donor and patient helps to lower the risk of GVHD. There are also medications that help prevent GVHD. Even with a close HLA match and medication, some people still get GVHD.

Allogeneic stem cell transplants for older patients or who have overall poor health are relatively uncommon. This is because the pre-transplant conditioning therapy is generally not well tolerated by such patients, especially those with poorly functioning internal organs. However, reduced intensity allogeneic stem cell transplants may be a treatment option for certain patients who are older, who have diseases that involve major organs, such as the heart or liver, or who are otherwise not healthy or strong enough to undergo standard allogeneic transplantation.

Reduced-intensity allogeneic stem cell transplantation

Reduced-intensity allogeneic stem cell transplantation (sometimes called a mini-transplant or nonmyeloablative transplant), similar to a standard allogeneic STC, uses stem cells from a donor, but the conditioning treatment contains lower, less toxic doses of chemotherapy, and radiation. This type of SCT may be an option for certain people who are older or who are otherwise not healthy enough or strong enough to undergo standard allogeneic SCT.

The success of reduced-intensity SCT depends on the graft-versus-tumor (GVT) effect of the donor stem cells rather than on high-dose treatments to kill the cancer cells. The goal is to have the donor stem cells take up residence in the recipient’s marrow and produce white blood cells that will attack the patient’s remaining cancerous blood cells.

Research shows that reduced-intensity allogeneic SCT may be effective in treating certain patients with chronic myeloid leukemia (CML); acute myeloid leukemia (AML); non-Hodgkin lymphoma (NHL); chronic lymphocytic leukemia (CLL); or myelodysplastic syndromes (MDS).

Possible complications 

Reduced-intensity allogeneic transplantations carry many of the same risks as standard allogeneic transplantations:

• A person's body may reject the donated stem cells before they are able to engraft in the bone marrow
• A person's immune cells may see the donor’s cells as foreign and destroy them before the donor stem cells can engraft (grow and make new blood cells in the patient’s body)
• GVHD