A haploidentical stem cell transplant uses healthy, blood-forming cells from a donor to treat certain blood cancers and disorders. As a form of allogeneic transplant, the donor and recipient are different people. The term “haploidentical” signifies the donor is a “half-match” to the patient, which is determined by proteins on cell surfaces called human leukocyte antigens (HLA).
This procedure is an option for patients with conditions like leukemia and lymphoma who need a transplant but cannot find a perfectly matched donor. Using a partially matched family member expands the potential donor pool considerably, making these transplants more accessible.
Understanding the Haploidentical Donor
Donors for a haploidentical transplant are first-degree relatives, such as parents, children, or siblings, who share exactly half of the patient’s HLA markers. Every person inherits half of their HLA markers from each parent, so a parent is always a half-match for their biological child, and vice versa. Siblings have a 50% chance of being a half-match.
This contrasts with traditional allogeneic transplants, which required a perfect or near-perfect HLA match. Finding such a donor can be a challenge, especially for individuals of diverse ethnic backgrounds or those with uncommon HLA types. Because close family members can serve as donors, the search for a suitable match is often much faster.
The Patient Transplant Journey
The transplant journey begins with a pre-transplant evaluation. This medical workup assesses the patient’s overall health and organ function to ensure they are physically prepared for the process. Following the evaluation, the patient begins the conditioning regimen. This phase uses high-dose chemotherapy and sometimes total body irradiation (TBI) to eradicate the underlying disease and suppress the patient’s immune system to prevent it from rejecting the donor cells. The intensity of conditioning varies, with nonmyeloablative regimens using lower doses and myeloablative regimens using more intensive therapy.
The donor’s stem cells are infused into the patient’s bloodstream through a central venous catheter in a process similar to a blood transfusion. The infused stem cells then travel to the bone marrow. After the infusion, the patient enters a waiting period known as engraftment. The transplanted stem cells settle into the bone marrow and begin producing new blood cells. A sustained rise in neutrophil counts, usually within two to three weeks, is the first sign of successful engraftment.
Managing the Immune Mismatch Post-Transplant
The genetic difference between a half-matched donor and the recipient increases the risk of two primary complications: graft rejection and Graft-versus-Host Disease (GVHD). Graft rejection is when the patient’s residual immune system attacks the donor cells. GVHD occurs when the newly engrafted donor immune cells recognize the patient’s body as foreign and begin to attack it, potentially causing inflammation and damage to various organs.
A major innovation that has made these transplants successful is post-transplant cyclophosphamide (PTCy). This chemotherapy drug is administered a few days after the stem cell infusion, typically on days +3 and +4. The timing allows the initial engraftment process to begin but targets the immune cells before they can mount a full-scale attack.
The mechanism behind PTCy is selective. When the donor’s immune T-cells encounter the patient’s tissues, the T-cells most likely to cause severe GVHD begin to proliferate rapidly. Cyclophosphamide is particularly effective at eliminating these rapidly dividing cells. Meanwhile, hematopoietic stem cells and regulatory T-cells, which help to promote tolerance, are less affected because they are not dividing as quickly. This targeted approach purges the most dangerous alloreactive T-cells while preserving the beneficial cells needed for engraftment and long-term immunity.
This strategy of administering high-dose cyclophosphamide after the transplant has dramatically reduced the rates of severe GVHD, making the procedure a much safer and more reliable option.
Long-Term Recovery and Outlook
Recovery after a haploidentical transplant involves a gradual rebuilding of the immune system. Full immune reconstitution is slow, with adaptive immunity taking one to two years to recover. While innate immune cells recover within the first few months, the more specialized T-cells and B-cells take much longer to mature.
During this prolonged immunodeficiency, patients are vulnerable to infections. Regular follow-up appointments are scheduled to monitor blood counts, check for signs of GVHD, and manage immunosuppressive medications. These drugs are tapered over many months as the new immune system learns to tolerate the patient’s body.
Patients are also monitored for potential long-term side effects from the conditioning therapy. The goal of the transplant is a cure and a return to a good quality of life. As the immune system strengthens, patients can gradually resume normal activities.