When a child is being considered for a stem cell transplant, one of the first steps is to find out whether a family member is a suitable donor. This involves special blood studies on the patient and his or her entire family. The standard test is called tissue typing, also referred to as human leukocyte antigen (HLA) or histocompatibility typing. A second test is called high resolution DNA typing.
Human Leukocyte Antigen Typing
HLA tissue typing is a blood test performed in order to identify the most suitable donor for a patient needing an allogeneic transplant. An antigen is a protein on the surface of the lymphocytes cells. The HLA antigens are crucial in the recognition of self and non-self. HLA antigens are determined by genes on chromosomes and passed to a child from each parent. Because each parent contributes a chromosome there are pairs of antigens. Tissue typing is a test that identifies HLA antigens. Two groups of HLA antigens are important to tissue typing: Class I antigens and Class II antigens. Within each group, antigens are evaluated for a possible match with your child. A perfect HLA match means that all of the donor HLA antigens typed are identical to the recipients.
The following is an example of an HLA report:
A25, B38(w4), Cw3, DR15 (DQ1, DR51) (inherited from mother)
A3, B7(w6), Cw7, DR14 (DQ1, DR52) (inherited from father)
Inheritance Pattern of HLA Characteristics
Each potential donor will be HLA typed and these results will be compared to the patient’s HLA type. A donor who matches all the patients HLA antigens is preferred. Because siblings inherit their HLA genes from the same parent a patient’s best chance of finding a donor is within his or her family. Each sibling has a 1 in 4 chance of matching the patient. For those without a family HLA match, a search for an unrelated donor will be performed through a two registries known as the National Marrow Donor Program (NMDP) and Cord Blood Registry (CBR).
A biologic parent is almost always half-matched, or haploidentical, which means half of the patient’s HLA matches with his or her parent. There is a 50 percent chance that any sibling will be haploidentical with any other sibling. Special preparation is necessary for haploidentical transplantation in order for a haploidentical stem cell transplant to work without resulting in a fatal graft-versus-host-disease (GVHD) reaction. The stem cells must be specially treated after they are collected from the donor and before they are transplanted into the patient. This treatment removes the donor T lymphocytes from the stem cells that cause GVHD. GVHD will be explained in greater detail later in this handbook.
There are advantages and disadvantages to removal of the T cells from the product. The technique that is used to remove the cells reduces the risk and severity of GVHD. However, there is an added risk that the stem cells might not engraft. In order to improve the chances for successful engraftment, additional treatment with radiation and chemotherapy is added to the conditioning regimen. In some cases, such as children with severe combined immunodeficiency disease (SCID), this is not done.
T cell depletion may also cause a delay in the recovery of the immune system, or the body’s defense against infection, resulting in a higher risk of infections after transplant. T cell depleted stem cells from a parent, sibling or close relative may be considered for children who do not have an HLA matched related or unrelated donor.
The majority of children with diseases that could be cured with a stem cell transplant will not have a matched related donor. For this reason, there are several alternative donor options.
- Unrelated Donor– When a related donor cannot be found a search for an unrelated donor is conducted. An unrelated donor an individual who is HLA matched with the patient, healthy and are willing to donate stem cells.
- Umbilical Cord Blood– If a matched unrelated marrow or stem cell donor is unavailable; another source of unrelated donor marrow stem cells is umbilical cord blood (UCB). There are many UCB banks worldwide which process and store cord blood. The cord blood, which is normally thrown away after the baby is born, contains stem cells. One potential advantage of using cord blood is that is does not have to be a perfect tissue match with the recipient. Another advantage is that there is no risk to the donor in the collection process. Disadvantages include the potential for an inadequate number of stem cells obtained during the collection. So for a large patient a large volume of cord blood would be needed and sometimes is not available. Also there is a relative delay in the recovery of marrow function post transplant.
Selecting the Allogeneic Donor
Your SCT doctor will select the donor based upon several things including choosing the best matched tissue typing to your child. Once the donor has been selected, he/she will need several blood tests to evaluate past exposure to different viruses such as cytomegalovirus (CMV), HIV and Hepatitis. For additional information on how the marrow is obtained from the donor, please see The Marrow Harvest section of this handbook.