What is engraftment after a stem cell transplant?

On transplant day, the new stem cells are given through a vein, much like a blood transfusion. They travel through the bloodstream to the bone marrow, the soft tissue inside bones. There they begin making new red cells, white cells and platelets. This is called engraftment. NMDP, which runs the US donor registry, calls it an important milestone in recovery.

Until then, the body has fewer white blood cells than normal. NMDP explains that this is when the risk of infection is highest. Conditioning, the treatment given before the transplant, has made space in the marrow and weakened the diseased cells. So the first weeks are a time of waiting and watching. Infection and bleeding are real risks, and transfusions of red cells and platelets are common. Anthony Nolan, a UK stem cell charity, says these transfusions are a normal part of recovery. They don’t mean the transplant hasn’t worked.

Engraftment is not the end of recovery. The immune system takes much longer to fully recover, the US National Cancer Institute says. It takes several months after a transplant with a person’s own cells, and 1 to 2 years after a donor transplant.

The transplant team checks blood counts often. NMDP says the team looks at white blood cells, the absolute neutrophil count (ANC), hemoglobin and platelets. Neutrophils are the most common kind of white blood cell, and they help fight infection. NMDP says white cells are the first to engraft, followed by red cells and platelets. Anthony Nolan says the first sign is often a rising white cell count.

In 2024, transplant groups from Europe, North America and the Asia-Pacific region agreed on shared definitions. Neutrophil recovery is the first of 3 days in a row with a neutrophil count of at least 500 per microliter of blood, after counts hit their lowest point. Platelet recovery is the first of 3 days in a row with a platelet count of at least 20,000 per microliter, with no platelet transfusion for 7 days in a row.

After a donor transplant, the team may also run chimerism tests. These show how much of the blood comes from the donor. Under the same 2024 definitions, full donor chimerism means more than 95% donor cells, and mixed chimerism means 5% to 95%.

NMDP says engraftment usually happens within the first 30 days after transplant, but sometimes takes longer. Anthony Nolan says it normally takes around two to three weeks. The American Cancer Society says the new stem cells start making white blood cells within the first 6 weeks.

Where the cells came from makes a difference. Stem cells collected from a donor’s bloodstream tend to engraft sooner than cells taken from the marrow. In a large trial of unrelated-donor transplants in the US and Canada, neutrophils recovered a median of 5 days sooner with blood stem cells than with marrow. Platelets recovered a median of 7 days sooner.

Cord blood usually takes longer. MedlinePlus explains that cord blood has fewer stem cells, so blood counts take much longer to recover. In a trial in the US and Canada of children and young people with blood cancers, neutrophils recovered a median of 21 days after one cord blood unit and 23 days after two. For some, it took far longer.

Some people get medicines called growth factors, usually as injections, to help engraftment happen more quickly, Anthony Nolan says.

Some things make it harder for new cells to take hold. The American Cancer Society lists a donor and patient who are not well matched, removing T cells from the donor cells before transplant, and a low number of stem cells, such as a single cord blood unit.

A study published in 2013 looked at 967 first donor transplants done from 1995 to mid-2010 at one center in Stockholm, Sweden. Graft failure was more likely when T cells had been removed from the graft or the HLA match was not full. It was also more likely with milder (reduced-intensity) conditioning and in people who did not have cancer. More donor cells lowered the risk.

Antibodies can matter too. Some patients have antibodies against the donor’s tissue type. These are called donor-specific antibodies. Guidelines from EBMT, the European transplant society, call them an important cause of graft failure, especially with half-matched (haploidentical) donors. The guidelines cover how to test for them and treat them.

Problems can also pull counts down after the new cells start working. A 2022 review linked poor graft function with cytomegalovirus (CMV), a common virus that can wake up again after transplant. It also linked it with graft-versus-host disease. Myelofibrosis, which scars the marrow, and a large spleen can make it harder for new cells to work, too. In one example in the 2024 definitions paper, the authors wrote that CMV, a CMV medicine and leftover leukemia may have helped cause a drop in counts.

Graft failure means the new stem cells don’t settle in the marrow and multiply as they should. The American Cancer Society says this can lead to serious bleeding or infection. It says graft failure is suspected when counts don’t start going up within 3 to 4 weeks of a marrow or blood stem cell transplant, or within 7 weeks of a cord blood transplant.

The 2024 shared definitions name a few kinds. Primary graft failure means neutrophils have not reached 500 per microliter by day 30 after a blood or marrow transplant, or by day 42 after cord blood, and all blood counts are low. Secondary graft failure means counts recovered and then fell, so the person again needs transfusions or growth factors. Poor graft function means the person keeps needing transfusions or growth factors with no other explanation, such as relapse, a medicine or an infection.

Graft failure is not very common, the American Cancer Society says. In the unrelated-donor trial in the US and Canada, it happened in 3 in 100 people who got blood stem cells and 9 in 100 who got marrow. At the Stockholm center, 54 of 967 people (5.6%) had graft failure. In most of them, the patient’s own marrow grew back instead of the donor’s.

Care teams have options. The American Cancer Society says a second dose of stem cells may be possible, if they are available. Anthony Nolan says doctors consider a second transplant for graft failure or relapse. For poor graft function, a 2022 review describes a top-up of selected donor stem cells given without new conditioning, and medicines that help the marrow make blood. It says these have worked with variable success. Which path fits depends on the illness, the donor and the person’s health.

As the new cells start working, some people develop engraftment syndrome. It is not an infection. It can cause fever, skin rash, diarrhea and fluid in the lungs. A 2022 review found it after both kinds of transplant, with a person’s own cells or a donor’s. In most of the studies it reviewed, doctors treated it with steroid medicine given through a vein.

Engraftment lowers the risk of infection, but it does not remove it, the American Cancer Society notes. People usually stay in the hospital, or visit the transplant center daily, until their counts start returning to normal. The society says this usually takes about 2 to 6 weeks.

After a donor transplant, follow-up goes on for months. Anthony Nolan says doctors regularly measure chimerism. The team also keeps watching for infection and graft-versus-host disease.