Donor search

The search for a histocompatible donor should be started as soon as HSC transplantation has become a therapeutical option.

Related donors

The best chance to find a matched donor is within the family. Because the HLA genes are inherited in haplotypes, a patient has a chance of 1:4 to be HLA-compatible with his sibling. HLA-A,B,DR low resolution typing (DNA-typing or serology) is usually sufficient to determine whether 2 siblings have inherited the same 2 HLA-haplotypes. The fact that low resolution typing techniques are not able to make out all the allelic variants in the population is not important, because these 2 siblings will have inherited the same allelic variants from their parents.

Unrelated volunteer donors

When no matched sibling donor is available, a search in one of the donor registries with millions of volunteer donors for the best matched unrelated donor can be performed. A very useful source is the BMDW Registry that contains most of the HLA data of the donors in the national registries.
The chance of finding another individual that expresses the same alleles for all loci would be infinitely small if the HLA alleles were randomly distributed in the population. However, because the HLA genes are all on the same chromosome, a strong linkage disequilibrium exists between the different loci. Furthermore, many HLA alleles are relatively infrequent. As a consequence, the frequency of a (common) haplotype in the population is much higher than it would have been if the loci were inherited independently. At present, the chance of finding a donor matched for HLA-A,-B,-C,-DR and -DQ is approximately percent.

The complication rates of transplants using matched unrelated donors are generally higher than with matched sibling transplants. Furthermore, the search process is time consuming. Many patients with aggressive diseases cannot wait the 2 to 4 months needed to locate the best-match unrelated donor for a transplantation.

The HLA typing strategy for unrelated donor is considerably different from the strategy for a related donor.

Cord blood

Cord blood is a rich source of HSC that can be harvested at birth and cryopreserved until it can be used for transplantation. At present, several cord blood banks can be searched to find a suitable (cord blood) donor. Obviously, cord blood banks containe far less cords than there are unrelated donors in the registries. Therefore, the degree of matching will be lower but because the immune system of the neonate is still immature, the T cells in the cord blood cause less severe GVHD so that an HLA-mismatch may be accepted.