HSCT stands for hematopoietic stem cell transplantation, a procedure that replaces damaged or destroyed bone marrow with healthy stem cells capable of producing new blood cells. It’s sometimes called a bone marrow transplant, though the stem cells can also come from other sources. HSCT is used to treat blood cancers like leukemia and lymphoma, certain immune disorders, and inherited blood diseases like sickle cell disease.
How HSCT Works
Your bone marrow is a factory that produces red blood cells, white blood cells, and platelets. When disease damages or corrupts that factory, whether through cancer, a genetic disorder, or an immune system gone haywire, HSCT essentially replaces it. Healthy stem cells are infused into your bloodstream, travel to your bone marrow, and begin producing new, functional blood cells in a process called engraftment.
The way this helps depends on the disease being treated. In blood cancers, the transplanted immune cells from a donor can recognize and attack remaining cancer cells, creating a powerful “graft versus leukemia” effect. In autoimmune diseases like multiple sclerosis, the transplant resets the immune system by restoring the regulatory function that keeps immune cells from attacking the body’s own tissues. In inherited conditions like sickle cell disease, the new stem cells simply produce healthy blood cells that the patient’s own marrow could not.
Autologous vs. Allogeneic Transplants
There are two main types of HSCT, and they differ in where the stem cells come from.
In an autologous transplant, your own stem cells are collected before treatment, stored, and then returned to you after intensive chemotherapy destroys both the cancer and your existing bone marrow. This avoids the risk of your body rejecting the transplant, since the cells are your own. The downside is that there’s no immune attack on remaining cancer cells, and relapse is more common over time.
In an allogeneic transplant, stem cells come from a donor, either a matched sibling, an unrelated volunteer, or a cord blood unit. This type carries the potential for a cure because the donor’s immune cells can hunt down and destroy cancer cells the chemotherapy missed. However, those same donor immune cells can also attack your healthy tissues, a complication called graft-versus-host disease. Allogeneic transplants also carry higher rates of infection and treatment-related mortality.
Where Stem Cells Come From
Stem cells for transplant can be harvested from three sources, each with trade-offs.
- Peripheral blood: The most common source today. Donors receive injections of a growth factor that pushes stem cells out of the bone marrow and into the bloodstream, where they’re collected through a process similar to blood donation. Peripheral blood transplants engraft faster, with white blood cell recovery occurring around day 15 compared to day 20 for bone marrow grafts. The trade-off is higher rates of graft-versus-host disease: chronic GVHD develops in about 22% of peripheral blood recipients versus 11% of bone marrow recipients.
- Bone marrow: Collected directly from the donor’s hip bones under anesthesia. Bone marrow grafts produce lower rates of both acute and chronic GVHD and, in conditions like aplastic anemia, significantly better overall survival (84% versus 68% for peripheral blood in one large analysis).
- Cord blood: Collected from the umbilical cord after a baby is born. Cord blood requires less precise donor matching, making it a valuable option for patients who can’t find a well-matched adult donor. The cell count is lower, which can mean slower engraftment.
Finding a Donor Match
For allogeneic transplants, the donor’s tissue type needs to closely match the recipient’s. This matching is based on proteins called human leukocyte antigens (HLA) found on the surface of your cells. These proteins help your immune system distinguish your own tissue from foreign invaders, so a poor match increases the risk that the donor cells will attack your body, or that your body will reject the graft entirely.
The ideal match is a sibling who shares the same HLA markers. Siblings are matched at six key HLA sites (HLA-A, B, and DRB1), and each sibling has roughly a 25% chance of being a full match. When no matched sibling is available, transplant teams search international registries for an unrelated donor matched at eight HLA sites (adding HLA-C). If an 8/8 match isn’t available, a 7/8 match with a single mismatch can be used with acceptable, though higher, risk.
A newer approach uses half-matched, or “haploidentical,” family donors. Since every biological parent and child shares at least half their HLA markers, this dramatically expands the donor pool. Haploidentical transplants require at least a 4/8 match with no more than one mismatch at any single site. The risk of graft failure is higher in this setting, particularly for patients whose immune systems have been sensitized by prior blood transfusions or pregnancies.
The Conditioning Phase
Before receiving new stem cells, you go through a conditioning phase: high-dose chemotherapy, sometimes combined with radiation, designed to destroy your existing bone marrow and suppress your immune system enough that it won’t reject the incoming donor cells.
Traditional “myeloablative” conditioning uses the highest tolerable doses to wipe out as much cancer as possible. This approach is effective but punishing on the body, producing significant organ toxicity that limits its use in older patients or those with other health problems. Since most blood cancers occur in people aged 65 to 70, this was a major limitation.
Reduced-intensity conditioning was developed in the 1990s to extend transplant to these patients. It uses lower doses that still suppress the immune system enough for donor cells to engraft, then relies on the donor immune system’s “graft versus leukemia” effect to eliminate remaining cancer over time. Reduced-intensity regimens cause less damage to the gut lining and organs, and carry a lower risk of bacterial infections during recovery. The risk of fungal infections and certain viral reactivations remains similar regardless of which conditioning approach is used.
What Recovery Looks Like
After the stem cells are infused, there’s a vulnerable waiting period while the new cells travel to your bone marrow and begin producing blood cells. During this time, your immune system is essentially nonexistent. White blood cell counts bottom out, leaving you highly susceptible to infections. You’ll typically remain in the hospital or in closely monitored outpatient care during this phase.
Engraftment, the point at which new stem cells begin producing measurable numbers of white blood cells, generally occurs around two to three weeks after transplant. Peripheral blood stem cells tend to engraft about five days faster than bone marrow grafts. Platelet recovery follows a similar pattern. Even after engraftment, your immune system remains deeply compromised for months. The first 100 days after transplant are considered the highest-risk period, and you’ll be monitored intensively for infections, organ complications, and signs of graft-versus-host disease.
Full immune recovery can take a year or longer. During this time, preventive medications protect against viral, fungal, and bacterial infections. Patients with chronic graft-versus-host disease may need ongoing immune-suppressing treatment for years, which carries its own infection risks.
Graft-Versus-Host Disease
GVHD is the most significant complication of allogeneic transplants. It occurs when donor immune cells recognize your tissues as foreign and mount an attack. Acute GVHD develops in up to 50% of patients receiving cells from an HLA-matched sibling, with higher rates from less well-matched donors.
Acute GVHD most commonly targets three areas. The skin is affected in about 70% of cases, typically starting as an itchy or painful rash on the palms, soles, and neck that can spread across the body. The gastrointestinal tract is involved in 74% of cases, causing persistent watery diarrhea, abdominal pain, nausea, and sometimes bloody stool severe enough to require transfusions. The liver is affected in 44% of cases, usually alongside skin or gut symptoms rather than on its own.
Chronic GVHD develops later, affects 6% to 80% of allogeneic transplant recipients depending on the donor source and other factors, and resembles autoimmune conditions like scleroderma. It can cause dry eyes, mouth sores resembling lichen planus, skin tightening, and lung problems. Chronic GVHD requires long-term immunosuppressive treatment, and recurrent infections during this treatment are a leading cause of death.
Conditions Treated With HSCT
HSCT is a standard treatment for a range of diseases. Acute myeloid leukemia is one of the most common indications. In children with high-risk AML, transplant roughly doubles five-year disease-free survival compared to chemotherapy alone (about 50% versus 26%). It’s also used for acute lymphoblastic leukemia, chronic lymphocytic leukemia with certain high-risk features, myelodysplastic syndromes, and various lymphomas, typically when initial treatments have failed or the cancer is aggressive enough to warrant it upfront.
Beyond cancer, HSCT treats inherited bone marrow failure syndromes like Fanconi anemia and dyskeratosis congenita, which can present in both children and adults. Severe aplastic anemia, where the bone marrow stops producing enough blood cells, is another well-established indication. For autoimmune diseases, HSCT is increasingly used in select cases of multiple sclerosis, systemic sclerosis, and other conditions where the immune system causes severe, progressive damage that conventional treatments can’t control.