A haploidentical stem cell transplant is a medical procedure that replaces unhealthy blood-forming cells with healthy ones from a donor. This type of transplant is considered a “half-match” because the donor’s human leukocyte antigens (HLA) are only about 50% compatible with the patient’s. Typically, a close family member such as a parent, child, or sibling serves as the donor. This broadens the possibilities for patients who might not otherwise find a fully matched donor.
Why Haploidentical Transplants Are Used
Haploidentical transplants help overcome the challenge of finding a fully matched donor, which can be particularly difficult for patients from diverse ethnic backgrounds. Only a fraction of patients, sometimes as low as 10% for Black patients or less than 5% for Asian patients, find a match through traditional donor registries. In contrast, nearly everyone has at least one haploidentical donor available within their immediate family, making this a widely accessible option. This immediate availability allows the transplant process to begin more quickly, beneficial for patients with aggressive diseases requiring urgent treatment.
This transplant is considered for various conditions, primarily certain blood cancers and disorders. These include leukemias, lymphomas, myelodysplastic syndromes, and bone marrow failure syndromes like aplastic anemia and sickle cell disease. While historically associated with higher risks, advancements in transplant techniques and post-transplant care have significantly improved outcomes. Proceeding with a transplant without a long search for a fully matched donor can be life-saving for many individuals.
The Transplant Process
The haploidentical stem cell transplant process begins with a conditioning regimen for the patient. This phase involves high-dose chemotherapy, and sometimes radiation therapy, to eliminate diseased cells and suppress the patient’s immune system. This prepares the bone marrow for new donor cells to engraft and prevents rejection. Conditioning can lead to side effects such as fatigue, hair loss, nausea, and mouth sores, which are managed by the medical team.
Following conditioning, the patient receives an infusion of healthy stem cells from the haploidentical donor. This infusion is similar to a blood transfusion, administered through a central venous catheter. The patient remains awake and typically experiences no discomfort. The stem cells travel to the bone marrow, where they begin to grow and produce new blood cells, a process called engraftment. Engraftment typically takes two to six weeks, with the patient monitored in the hospital.
Stem cells for transplantation can be collected from the donor in a few ways: bone marrow, peripheral blood, or umbilical cord blood. Peripheral blood stem cell collection, known as apheresis, is a common method where the donor receives injections of granulocyte colony-stimulating factor (G-CSF) for several days to move stem cells from the bone marrow into the bloodstream. The blood is then passed through a machine that separates the stem cells, and the rest of the blood is returned to the donor. If bone marrow is chosen, it is collected from the donor’s hip bones under general anesthesia. Umbilical cord blood, collected at birth, is another source, though it typically contains fewer stem cells and may lead to slower recovery.
Managing Risks and Recovery
Haploidentical transplants carry specific risks that require careful management. A primary concern is graft-versus-host disease (GVHD), where the donor’s immune cells recognize the patient’s tissues as foreign and attack them. This risk is higher due to the partial HLA mismatch. To mitigate GVHD, post-transplant cyclophosphamide (PTCy) is commonly used. PTCy selectively depletes donor T-cells responsible for GVHD while allowing beneficial immune cells to survive and promote engraftment.
Infections are another significant risk, particularly when the patient’s immune system is severely suppressed after transplant. Patients are susceptible to bacterial, viral, and fungal infections. Common viral reactivations include cytomegalovirus (CMV) and BK virus, which can cause hemorrhagic cystitis. Prophylactic medications, rigorous monitoring, and prompt treatment are used to prevent and manage these infections. Immune recovery is a gradual process, with neutrophils and phagocytes recovering within about one month, T cells in six to twelve months, and B cells taking twelve to twenty-four months.
The recovery period after a haploidentical transplant is extensive, often involving an initial hospital stay of around 40 days, followed by recuperation at home. Patients require ongoing post-transplant care, including immunosuppressive medications to prevent GVHD, regular monitoring of blood counts and organ function, and lifestyle adjustments to minimize infection risk. Long-term follow-up with the transplant team manages potential late complications, such as chronic GVHD, and monitors for disease relapse. While the long-term anti-cancer effect is still being studied, current outcomes are comparable to those of fully matched transplants.