A bone marrow transplant (BMT) replaces a patient’s unhealthy or destroyed blood-forming cells with healthy stem cells. This treatment is necessary for individuals suffering from conditions like leukemia, lymphoma, severe aplastic anemia, or certain immune deficiency disorders. The procedure involves first eliminating the patient’s diseased cells, usually through high-dose chemotherapy or radiation, and then infusing the donor’s healthy cells intravenously, much like a blood transfusion. These healthy stem cells travel to the bone marrow cavity, where they begin producing new, functional blood cells. Finding a compatible donor whose cells the patient’s body will not reject is essential for success.
Understanding HLA Compatibility
The search for a suitable donor centers on matching specific proteins called Human Leukocyte Antigens (HLA), which act as identification markers on the surface of most cells. These antigens allow the immune system to distinguish its own cells from foreign invaders. A close match in the HLA profile is necessary to prevent the donor’s immune cells from attacking the recipient, a serious complication known as Graft-versus-Host Disease (GVHD). Compatibility also impacts the risk of the patient’s body rejecting the new stem cells, which is called graft failure.
HLA genes are inherited in blocks, called haplotypes, with one haplotype coming from each parent. A complete match involves identity across multiple HLA loci, typically eight to twelve markers, which determine the transplant outcome. Since a child inherits half of their HLA markers from each parent, this inheritance pattern explains why certain relatives are more likely to be a match. High-resolution DNA typing determines the exact sequence of these genes, providing the most detailed assessment of compatibility. The more antigens that match, the better the engraftment of the donated cells.
The Familial Donor Hierarchy
The search for a donor begins within the patient’s immediate family due to the high probability of genetic overlap. Full siblings offer the best chance of a perfect HLA match, with a 25% probability of inheriting the exact same two haplotypes. An HLA-identical sibling is the preferred source for an allogeneic transplant because of the superior clinical outcomes associated with this level of matching.
If a fully matched sibling is unavailable, the search extends to parents and children, who are always at least a half-match, known as haplo-identical. This occurs because every child inherits one of the two haplotypes from each parent, guaranteeing a 50% match at the relevant loci. Advances in medical protocols allow for successful haplo-identical transplants, making a parent or child a common and rapidly available alternative donor source. Other extended relatives, such as aunts, uncles, or cousins, may also be considered, though the probability of a high-level match drops significantly.
Comprehensive Donor Evaluation
Once a family member is identified as a potential match through initial HLA testing, they undergo an extensive medical evaluation to confirm their suitability and safety as a donor. This process begins with detailed, high-resolution HLA typing to confirm the precise degree of compatibility. Medical teams perform a comprehensive physical examination and take a complete medical history to ensure the donor is in good health and can safely undergo the procedure.
The evaluation includes blood tests to screen for infectious diseases, such as HIV, Hepatitis B and C, and Cytomegalovirus (CMV), which could be transmitted to the recipient. Diagnostic tests, including an electrocardiogram (EKG) and chest X-ray, are performed to assess heart and lung function. Potential donors also participate in counseling sessions, where they are informed about the risks and procedural details to ensure they provide informed consent before the donation.
The Donation Procedures
Stem cells can be collected from a family donor through two primary methods: Peripheral Blood Stem Cell (PBSC) donation or a surgical bone marrow harvest. PBSC donation is the more common, non-surgical, outpatient procedure today. For five days leading up to the collection, the donor receives injections of filgrastim (G-CSF), which prompts the bone marrow to release stem cells into the bloodstream.
The collection is performed through apheresis, where blood is drawn from one arm, passed through a machine that filters out the stem cells, and the remaining blood is returned to the donor through the other arm. Donors may experience mild, flu-like symptoms, bone pain, or muscle aches from the G-CSF injections, which subside shortly after the donation is complete.
The alternative, a surgical bone marrow harvest, is performed in an operating room under general or spinal anesthesia. During the harvest, a liquid sample of bone marrow is withdrawn using needles inserted into the back of the pelvic bone. This procedure usually takes one to two hours, and most donors are discharged the same day or after an overnight stay. Recovery involves mild discomfort, such as back or hip pain and soreness at the collection site, managed with over-the-counter pain relievers. The medical team chooses the method based on the patient’s disease and which stem cell source offers the best chance for a successful outcome.