When a child is being considered for a bone marrow transplant, one of the first steps if 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, which has recently been developed, is called high resolution DNA typing.
These tests gauge how much the donor and recipient cells will recognize one another as the same or different. The greater the differences in the HLA typing, the greater the chance that either the donor's cells will not grow in the recipient — resulting in rejection or graft failure, or they will attack the recipient and cause a reaction called graft-versus-host disease (GvHD).
Optimal donors — Identical tissue typing
The optimal donor is a histocompatible (HLA) matched relative who is usually a sibling or, in rare cases, a parent or grandparent with identical HLA tissue typing. Everyone inherits two sets of chromosomes containing HLA genes, four genes per set. One set comes from their father and one from their mother, for a total of eight genes. There is a one in four, or 25 percent, chance that any brother or sister will have inherited the same two sets of HLA genes as the patient. For a parent to be "matched" with his or her child, both parents must by chance have some HLA genes in common with each other. It is very unlikely, about a one in a million chance, for two unrelated individuals to have the same HLA genes in common, and there is only a one in 200 chance that a parent and child will be HLA matched.
Optimal Donors -- Identical Tissue Typing
Partially-matched donors
A biologic parent is always half matched, or haplocompatible, which means four out of eight HLA match, with his or her child since each child inherits half of the HLA genes from each parent. There is a 50 percent chance that any sibling will be haplocompatible with any other sibling.
In order for a haplocompatible bone marrow transplant to work without resulting in a fatal 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 depletes them of the donor T lymphocytes that cause GvHD.
There are advantages and disadvantages to T cell depletion. The technique that is used at the UCSF Benioff Children's Hospital BMT Program significantly reduces the risk of GvHD both in terms of its chances of occurring, as well as its severity if it does occur.
However, there is an added risk that the marrow might not engraft. In order to improve the chances for successful engraftment, additional treatment with radiation and chemotherapy must be added to the conditioning regimen in most cases. This is not done with children who have severe combined immunodeficiency disease (SCID).
Also, there may be 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 bone marrow stem cells from a parent, sibling or other close relative may be considered for children who do not have an HLA-matched related or unrelated donor.
For more information about this special program at UCSF Benioff Children's Hospital, please see Haplocompatible Donor Program.