What is a donor lymphocyte infusion (DLI)?

Lymphocytes are white blood cells that help fight infection. T cells are one kind. In a DLI, lymphocytes collected from the patient’s stem cell donor are given into the bloodstream, in a much smaller amount than the transplant itself. Anthony Nolan, a UK stem cell charity and donor registry, calls it a “top-up” of these cells.

A DLI only follows an allogeneic, or donor, transplant, and it uses cells from that same donor. The US National Cancer Institute (NCI) describes it as lymphocytes from a donor given to a patient who has already had a stem cell transplant from the same donor.

It builds on the graft-versus-leukemia effect. After a donor transplant, NCI explains, the donor’s white blood cells can attack cancer cells that are left in the body. A DLI adds more of those cells to strengthen that attack. The first report of a DLI bringing back remission came in 1990, in people whose chronic myeloid leukemia had returned.

To treat relapse. When a blood cancer comes back after a donor transplant, a DLI is one option. The American Cancer Society says some people may be helped by white blood cells from the same donor and that a second transplant is sometimes possible. When a larger amount of disease has come back, Anthony Nolan says, doctors give chemotherapy first and then a DLI.

Before a full relapse. Very sensitive tests can find tiny amounts of cancer, called measurable residual disease (MRD), before regular tests can. Giving a DLI at this early warning sign is called preemptive DLI. For some people at high risk of relapse, the team plans a DLI before the transplant, to give afterward even with no sign of disease. This is called prophylactic, or preventive, DLI.

For mixed chimerism. Chimerism tests show how much of the blood comes from the donor. If the donor share stays low or keeps dropping, Anthony Nolan says, there is a risk of relapse or graft failure, and a DLI may push it up. A drop does not always mean relapse, and not everyone reaches 100% donor cells.

After transplants for conditions that are not cancer. DLI has also been used for mixed chimerism after a transplant with milder conditioning. In a US study of 27 children with such conditions, 7 reached lasting full donor chimerism after DLI alone. Others stayed mixed or needed more treatment, such as a stem cell boost or a second transplant.

Results depend a great deal on the illness and on how much disease there is. A 2024 review from Dana-Farber Cancer Institute looked at studies of DLI for chronic myeloid leukemia (CML) that came back after transplant. Complete response rates were 60 to 80 percent. For other blood cancers, response rates were about 20 to 30 percent. These included acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), multiple myeloma and non-Hodgkin lymphoma.

DLI tends to work better when there is less disease. A German center studied adults with AML who had transplants from 2009 to 2017. Those who started DLI early, guided by warning signs in tests, lived a median of 40.9 months. Those who got DLI only after a full relapse lived a median of 10.4 months. This was not a randomized trial, so the two groups may have differed in other ways too.

The effect is not immediate. A 2010 review said that in CML, some response usually shows in 2 to 3 months but may take up to a year. For acute myeloid leukemia (AML) that comes back, the same review said a DLI alone is not effective. Chemotherapy is needed to lower the amount of disease first.

The main risk is graft-versus-host disease (GVHD). This is when the donor cells attack the patient’s healthy tissues, such as the skin, liver and gut. Anthony Nolan says it can happen in the weeks after the infusion. A 2010 review reported GVHD in about 50 to 60 percent of people who received a DLI.

Anthony Nolan says giving a DLI in increasing doses over a period of weeks is one way to control that risk. A 2024 review describes European (EBMT) guidance. Infusions are usually spaced about four weeks apart, with up to three or four in total. Lower starting doses may be used when a DLI is given to prevent relapse or at an early warning sign.

A European registry study looked at adults with acute leukemia in remission who got preventive or preemptive DLI. Of them, 31 in 100 developed chronic GVHD, and 6 in 100 died from GVHD caused by the DLI. The risk was higher with age 60 or older, advanced disease at transplant, a shorter time since transplant and earlier acute GVHD.

A DLI can also cause a period of very low blood counts, called aplasia. This raises the risk of infection and bleeding. The 2010 review reported it in 20 to 40 percent of patients in earlier studies. It said most people’s counts recover on their own, with support in the meantime.

Sometimes the donor doesn’t need to do anything more. When enough lymphocytes are collected at the first donation, Anthony Nolan explains, doctors can freeze and store part of it for a later DLI. A German transplant center has reported using frozen portions of the original donation this way.

If not, the donor may be asked for a second donation. Anthony Nolan, the UK registry, tells its donors that a lymphocyte top-up happens in about 15% of patients. DKMS, an international donor registry, calls this a mononuclear cell (MNC) donation. It says its staff contact the donor to arrange it. DKMS also says doctors may ask for these cells to prevent relapse, fight an infection or help engraftment.

A lymphocyte donation is like a blood stem cell donation by apheresis, where a machine collects cells from the blood and returns the rest. But the donor does not get the injections used to move stem cells into the blood. Anthony Nolan says it takes about 4 to 5 hours on a single day, and donors usually recover in 1 to 2 days.

The donor has a new health check first. Anthony Nolan tells donors they are under no obligation to donate again. For their safety, it also limits how many times a donor gives. DKMS says a new exam may be needed. From a donor’s fourth MNC donation on, a DKMS medical advisor must approve it.

Experts writing for EBMT, the European transplant society, note that a half-matched (haploidentical) relative is in most cases easy to reach. Collecting the cells is also faster than from an unrelated registry donor.

Every unrelated donor starts by joining a registry. When someone joins the NMDP Registry, NMDP says, they give a cheek swab. The lab uses it to find their tissue type. They could be matched with a patient soon after joining, many years later or never.

When a donor is matched, NMDP says, it asks about their current health and checks that they are still interested in donating. A donor who gives stem cells may, less often, be asked later to help the same patient again with a lymphocyte donation, as described above.

The Jada Bascom Foundation does not enroll donors, test tissue types or collect cells. It helps people find the official registry where they live. The registry handles joining, matching and every donation, including any second donation for the same patient.