A bone marrow transplant, also known as a hematopoietic stem cell transplant, is a medical procedure that replaces a patient’s diseased or damaged bone marrow with healthy blood-forming stem cells. This treatment is often used for life-threatening conditions like leukemia, lymphoma, and other blood disorders. To ensure the patient’s body accepts the new cells, finding a compatible donor is the first and most immediate necessity, with the search beginning within the patient’s own family. The success of the transplant hinges on how closely the donor’s immune system matches the recipient’s, a compatibility measured by specific genetic markers.
The Critical Role of HLA Matching
Compatibility for a bone marrow transplant is determined by Human Leukocyte Antigens (HLA), which are proteins found on the surface of most cells in the body. These antigens are a fundamental part of the immune system, allowing it to distinguish between the body’s own cells and foreign invaders, such as bacteria or viruses. If the donor’s and recipient’s HLA markers do not align, the transplanted cells may recognize the recipient’s body as “foreign” and launch an attack, a severe complication known as Graft-versus-Host Disease (GVHD).
HLA markers are inherited from parents, with a child receiving half of their markers from their mother and half from their father. A high-resolution HLA test is performed to compare the markers across multiple gene locations, often aiming for a 10/10 or 12/12 match for the best outcome. Because of this inheritance pattern, family members are genetically predisposed to have a higher chance of sharing these markers.
Primary Family Donor Candidates
The most likely source of a perfect tissue match is a full sibling, meaning a brother or sister who shares both biological parents with the patient. Due to the way HLA genes are inherited, there is a one-in-four, or 25%, chance that any two full siblings will have inherited the exact same combination of HLA markers from both parents. This complete genetic sharing is referred to as an HLA-identical or fully matched sibling.
A fully matched sibling donor represents the optimal scenario for a transplant because it significantly reduces the risk of serious complications, particularly the severity of GVHD. Allowing the body to accept the new stem cells with minimal immune rejection. While the probability is 25% for each sibling, the presence of an HLA-identical sibling offers the best possible starting point for a successful allogeneic transplant.
Secondary Family Donor Candidates
When a fully matched sibling is unavailable, the search expands to other first-degree relatives who may provide a partial match, which is known as a haploidentical transplant. A haploidentical donor shares exactly half of the patient’s HLA markers, typically a 5/10 or 6/12 match, and is always a biological parent or child of the patient. This is because every child receives one half-set of HLA genes from each parent, guaranteeing a 50% match with either one.
Advancements in immunosuppressive therapies, such as the use of post-transplant cyclophosphamide, have made these half-matched transplants a viable and increasingly common option. While less ideal than a full match, this technique expands the donor pool to nearly all patients who have a first-degree relative available. Extended relatives, such as half-siblings, aunts, uncles, or cousins, may also be considered, though their likelihood of being a sufficient haploidentical match decreases rapidly.
Health and Screening Requirements for Donors
Regardless of their genetic relationship, any potential family donor must pass a thorough medical and psychological screening to ensure the safety of both the donor and the recipient. The donor must be in general good health, typically falling within an age range of 18 to 60, although these limits can vary. The screening process rules out the presence of serious chronic illnesses, such as certain types of heart disease or unmanaged diabetes, and infectious diseases, including HIV or Hepatitis B and C.
The initial evaluation involves a detailed medical history, a physical examination, and extensive blood and urine tests to assess the function of vital organs like the kidneys and liver. A psychological assessment is also conducted to ensure the donor is fully informed and capable of giving voluntary and unpressured consent to the procedure.