Bone marrow transplantation, also known as hematopoietic stem cell transplantation, is a medical procedure that replaces unhealthy blood-forming cells with healthy ones. This treatment is often used for individuals with various conditions, including certain cancers like leukemia and lymphoma, as well as specific genetic diseases or bone marrow failure syndromes. The success of a bone marrow transplant relies heavily on donor-recipient compatibility. This complex biological matching process helps minimize complications, such as the recipient’s immune system attacking the transplanted cells or the transplanted cells attacking the recipient’s body.
The Genetic Basis of Matching
Bone marrow matching primarily focuses on human leukocyte antigens (HLAs), proteins found on the surface of most body cells. These HLA proteins help the immune system distinguish between the body’s own cells and foreign invaders. The HLA system, located on chromosome 6, is the most diverse genetic system in humans, with many variants.
HLA genes are broadly categorized into Class I (HLA-A, HLA-B, HLA-C) and Class II (HLA-DR, HLA-DQ, HLA-DP). An individual inherits a set of HLA genes, called a haplotype, from each parent, expressing HLA molecules from both. This co-dominant inheritance contributes to the diversity of HLA types, making precise matching challenging.
The Matching Process
Determining an HLA match involves genetic testing, typically using blood or cheek swab samples from the patient and potential donors. This process, known as HLA typing, identifies an individual’s specific HLA genes. Molecular methods analyze HLA gene DNA sequences for precise allele identification.
Achieving an “allele-level” match, identifying precise genetic sequences of HLA genes, is important for successful transplantation. High-resolution typing is performed for key HLA loci, such as HLA-A, HLA-B, HLA-C, and HLA-DRB1. If a suitable family donor is not found, national and international registries, like the National Marrow Donor Program (NMDP) or Be The Match, facilitate searches for unrelated donors.
Donor Sources and Matching Probability
Potential bone marrow donors typically come from two main sources: related and unrelated. Siblings are often the first choice because they have the highest chance of a perfect HLA match due to shared genetic heritage. However, even full siblings only have a 25% chance of a perfect HLA match, as each child inherits a random combination of HLA genes from their parents.
For most patients without a suitable family match, unrelated donors are sought through large registries. Finding a perfect match (often defined as an 8/8 or 10/10 antigen/allele match across specific HLA loci) can be difficult, especially for patients from diverse ethnic backgrounds due to the wide variation in HLA types globally. While about 70% of Caucasians may find a suitably matched unrelated donor, the likelihood can be significantly lower for individuals of non-Caucasian descent.
Alternative Matching Strategies
When a fully matched donor is unavailable, alternative transplant options exist. Haploidentical transplants, often called “half-matched” transplants, are a common alternative. These involve a donor who is a 50% genetic match, such as a parent, child, or sibling. Advances in post-transplant care, including specific immunosuppressive therapies, have made haploidentical transplants safer and more frequently used.
Another alternative is umbilical cord blood transplantation. Cord blood contains hematopoietic stem cells and requires less stringent HLA matching than adult bone marrow. Cord blood units are selected based on factors like cell dose and HLA match, with a minimum 4/6 HLA match often acceptable, though 8-allele matching is increasingly preferred. Cord blood banks store these units, providing a viable option for patients, particularly children, who lack a fully matched donor.