Hematopoietic stem cell transplantation, commonly referred to as a bone marrow transplant, is a medical procedure used to replace a patient’s diseased blood-forming cells with healthy ones. This treatment is necessary for individuals with life-threatening conditions, such as blood cancers (leukemia and lymphoma) and some immune system disorders. The process involves suppressing the patient’s existing bone marrow, typically through chemotherapy or radiation, and then infusing healthy stem cells from a donor. Success depends on the patient’s immune system accepting the donor cells, making genetic compatibility the most significant first step in the process.
The Science of Matching
Donor compatibility relies on Human Leukocyte Antigens (HLA), proteins found on most cells that the immune system uses to distinguish between the body’s own cells and foreign invaders. A close match of these HLA markers is required to prevent graft-versus-host disease, a complication where donor immune cells attack the patient’s body. HLA matching focuses on comparing specific genes inherited from both parents.
The standard for a high-resolution match involves comparing 10 alleles across five key HLA loci (A, B, C, DRB1, and DQB1), aiming for a 10/10 match. In some cases, two additional markers (DPB1) are also analyzed for a 12/12 match, which can offer improved outcomes, especially for patients with early-stage disease. Since HLA markers are inherited, the chance of finding a perfect match is highest among family members who share a genetic background.
Donor Sources Hierarchy
The search for a donor follows a specific progression, beginning with the closest genetic relatives. An identical twin, who shares the exact same genetic makeup, represents the most ideal syngeneic match. If a twin is unavailable, the search focuses on full siblings, who have a 25% chance of inheriting the exact same HLA markers from both parents.
Approximately 70% of patients do not have a fully matched sibling donor available. When family options are exhausted, the medical team initiates a global search for a Matched Unrelated Donor (MUD). This involves accessing vast international donor registries that catalogue the HLA types of millions of volunteer donors worldwide.
Navigating the Donor Registries
Finding an unrelated donor is systematic and relies on large, international donor registries. These organizations maintain databases of volunteer donors who have provided an initial sample for HLA typing. The transplant center submits the patient’s detailed HLA profile to identify potential matches who share the required 10/10 or 12/12 markers.
The registry search operates in phases, starting with a preliminary electronic screen of the entire database. Potential matches are then contacted for confirmation typing and medical screening. This step ensures the initial HLA typing is accurate and that the donor is healthy and medically cleared to proceed. Donor diversity is significant because HLA types are inherited based on ancestry, meaning patients from less represented ethnic backgrounds often face a greater challenge finding a fully matched unrelated donor.
Alternative Matching Strategies
When a fully matched unrelated donor cannot be identified, transplant physicians consider several advanced alternative strategies.
Haploidentical Transplant
One common option is a haploidentical transplant, which uses a donor who is only a half-match. Since a child inherits precisely half of their HLA markers from each parent, a parent or child is always a haploidentical donor option. This approach has become increasingly viable due to advancements in post-transplant care. Specifically, the use of high-dose cyclophosphamide helps prevent severe graft-versus-host disease despite the HLA mismatch, making this a safer option than in the past.
Cord Blood
Another option is to use stem cells collected from umbilical cord blood, which is stored in public banks. Cord blood units have less stringent HLA matching requirements than adult donors because the immune cells are less mature. However, a drawback is the limited number of stem cells available in a single cord blood unit, which can result in slower engraftment. This source is often preferred for pediatric patients or smaller adults due to the cell count limitations.
Mismatched Unrelated Donor (MMUD)
A third strategy involves the use of a Mismatched Unrelated Donor (MMUD), where the donor and patient have one or two HLA mismatches. Although this option carries a greater risk of complications, such as graft-versus-host disease, it significantly expands the donor pool for patients who might otherwise have no available match. The selection among these alternatives—haploidentical, cord blood, or MMUD—is often based on the patient’s specific disease, the urgency of the transplant, and the transplant center’s experience with each procedure.