A bone marrow transplant is indicated for several malignant and non-malignant disorders. The process begins by identifying an appropriate donor by doing a test called tissue typing or human leukocyte antigen (HLA) histocompatability typing of immediate family members initially using serologic techniques. These tests try to determine 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 donors cells will not grow in the recipient resulting in rejection or graft failure (non-engraftment), or they will attack the recipient and cause a reaction called graft versus host disease (GVHD).
HLA are proteins found on the surface of almost all cells in the body that contain a nucleus being highest in concentration on the surface of white blood cells. HLA antigens are the major determinants used by the body's immune system for recognising and differentiating ‘self’ from ‘non-self’ (foreign) substances.
Each person has unique HLA antigens (although identical twins may match each other). There are many different major histocompatibility (HLA) proteins and individuals possess only a small, relatively unique set that is inherited from their parents. 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. There is a 50 percent chance that any sibling will be haplocompatible with any other sibling. 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. 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.
Routine testing involves checking for 6 antigens among family members. A fully matched family member is the most compatible match as both the recipient and donor often shares minor HLA antigens not usually included in testing. For transplant, class I and class II HLA antigen compatibility is tested and compared. Class I includes HLA-A, HLA-B, and HLA-C. Class II includes HLA-DR, HLA-DP, and HLA-DQ. A 6-of-6 match refers to testing of HLA-A, HLA-B, and HLA-DR, each of which has 2 alleles. If the donor and recipient is not a 6-of-6 match, they are said to be mismatched. When only 3 of 6 mismatch, the term of haplotypic donor applies. When a related donor cannot be identified, an unrelated donor may be used. An unrelated-donor search generally looks for 6-of-6 matches by performing a DNA-HLA typing which is more accurate than the serologic method. This data is stored in marrow donor registries and cord blood banks.