Bone marrow, a soft and spongy tissue found inside bones, plays a central role in the body’s health. It serves as the primary factory for producing various blood components, including red blood cells that carry oxygen, white blood cells that fight infections, and platelets that enable blood clotting. When bone marrow is diseased or damaged, it can no longer produce healthy blood cells, leading to severe and life-threatening conditions such as certain cancers or blood disorders. In such cases, a bone marrow transplant, which involves replacing the unhealthy marrow with healthy blood-forming stem cells, can offer a chance for recovery. For this life-saving procedure to be successful, finding a suitable “match” between the patient and a donor is important.
Why Matching is Crucial
The necessity of a precise match in bone marrow transplantation stems from the body’s immune system, which constantly works to distinguish between its own cells (“self”) and foreign invaders (“non-self”). If transplanted bone marrow cells are perceived as foreign, the recipient’s immune system will mount an attack. This immune response can lead to serious complications, including graft rejection, where the patient’s body destroys the new cells, or graft-versus-host disease (GVHD).
Graft-versus-host disease occurs when immune cells within the donated bone marrow or stem cells recognize the recipient’s body as foreign and attack its tissues and organs. Conversely, graft rejection happens when the recipient’s remaining immune cells attack the donor cells, preventing them from establishing themselves and producing new blood cells. Both rejection and severe GVHD can reduce transplant success and impact patient outcomes, highlighting the importance of a close match.
The Role of HLA Markers
The ability of the immune system to differentiate between self and non-self depends on specific proteins called Human Leukocyte Antigens (HLA) markers. These markers are found on the surface of most cells and serve as unique identifiers. The HLA system is highly diverse, with thousands of possible variations, making it challenging to find identical matches between unrelated individuals.
HLA genes are inherited from parents, with each parent contributing one set of HLA markers, known as a haplotype, to their offspring. This inheritance pattern means that siblings have a 25% chance of being a perfect HLA match, a 50% chance of being a half-match, and a 25% chance of sharing no HLA haplotypes. Because of this genetic sharing, a patient’s siblings are often the first candidates considered for a bone marrow transplant.
HLA markers are categorized into different classes, with Class I (HLA-A, -B, -C) and Class II (HLA-DR, -DQ, -DP) being the most significant for transplantation. Doctors typically evaluate 10 to 12 specific HLA markers to determine compatibility. A closer match across these markers significantly improves transplant success. The complexity and variability of HLA types underscore the challenge of finding a fully matched unrelated donor.
Finding a Compatible Donor
When a patient needs a bone marrow transplant and a fully matched family donor is not available, the search extends to unrelated donors through national and international registries. Organizations like Be The Match maintain large databases of potential donors with typed HLA markers. The process involves volunteers providing a cheek swab or blood sample, which is then analyzed to determine their unique HLA profile and added to the registry.
When a patient requires a transplant, their HLA type is compared against the profiles in these registries to identify potential matches. The likelihood of finding a suitable unrelated donor varies significantly depending on the patient’s ethnic background. Certain ethnic groups possess more diverse or unique HLA types, making it harder to find a match within the current donor pool. For instance, the chance of finding a match varies significantly by ethnic background, with white patients in the U.S. having a higher likelihood than African American or Hispanic/Latino patients. Increasing the diversity within donor registries is important to improve the chances of finding matches for all patients, particularly those from underrepresented ethnic backgrounds.
Alternative Transplant Options
In situations where a fully matched unrelated donor cannot be found, alternative transplant options may be considered. One such option is a haploidentical transplant, which uses a partially matched family member, often a parent or child. These donors share half of their HLA markers with the patient, making them a “half-identical” match. Advances in medical techniques, including specialized immunosuppressive therapies, have improved haploidentical transplant outcomes, allowing the body to better accept the partially matched cells.
Another alternative is umbilical cord blood transplantation. Cord blood, collected from the umbilical cord and placenta after birth, contains hematopoietic stem cells. It requires a less stringent HLA match compared to bone marrow or peripheral blood stem cell transplants. However, cord blood units typically contain a lower number of stem cells, which can lead to a slower engraftment process, particularly for adult patients. Despite this, umbilical cord blood offers a readily available source of stem cells that can be stored and accessed quickly for patients in need.