Haploidentical transplant: when a half-match can work

Doctors match patients and donors using HLA, the tissue-type markers found on most cells. HLA genes are inherited, half from each parent. A haploidentical donor is a relative who matches exactly half of the patient’s HLA.

A haploidentical transplant is a kind of allogeneic, or donor, transplant. NMDP, which runs the US national donor registry, says it is commonly used when a closely matched donor isn’t available. It is used for blood cancers such as acute myeloid leukemia, and for other diseases such as sickle cell disease.

For the donor, nothing is different. A half-matched relative donates the same way as a fully matched donor: either stem cells from the blood or marrow from the hip bone. The transplant doctor chooses which is best for the patient.

NMDP notes that because this approach is newer, not all transplant centers have experience with it, and not every hospital offers it.

Parents and children are always a half-match for each other. Each brother or sister has a 1 in 2 chance of being a half-match. NMDP says cousins, aunts and uncles are much less likely to be one. US guidelines note that testing the wider family can often find more half-matched relatives.

US guidelines published in 2025 by NMDP and CIBMTR, a transplant research group, say a half-matched donor can be found for most patients. Some patients still have no suitable relative. Others have only relatives who are older or have less favorable traits.

When there is a choice, teams look beyond the match. The guidelines recommend favoring younger donors. They also recommend testing the patient’s blood for antibodies against a donor’s HLA, and not using a donor who is the target of strong antibodies. These antibodies are more common in women who have been pregnant. So a mother may carry antibodies against her own child’s cells, which matters when her child is the donor.

NMDP says related donors, including half-matched ones, are generally able to donate sooner than unrelated donors. They are also usually easier to ask again if more cells are needed.

A large mismatch makes two immune systems react to each other. Donor immune cells called T cells can attack the patient’s body. This is graft-versus-host disease (GVHD). The patient’s immune system can also reject the new cells, so they never take hold. This is one cause of graft failure.

Early half-matched transplants removed most T cells from the graft in a lab. A 2024 history from Johns Hopkins explains that this lowered GVHD. But it came at the cost of more graft failure, more relapse (the disease coming back) and more deaths from other causes.

Researchers at Johns Hopkins in Baltimore tried another idea. After the new cells are given, the patient receives a high dose of cyclophosphamide, a chemotherapy drug. In their 2008 study, it was given on the third day after the transplant, or on the third and fourth days. Scientists are still learning exactly how it works. The drug acts most on cells that are dividing fast. It seems to remove or weaken many donor T cells that react against the patient. Regulatory T cells, which help calm the immune system, are relatively spared. This is post-transplant cyclophosphamide, or PTCy.

In the 2008 report on 68 patients, the donor cells did not take hold in 9 of the 66 who could be checked, and 1 of them died from it. Severe acute GVHD developed in 6%. US guidelines say PTCy was then widely adopted in a short time, because it is easy to give and relatively low in cost. It is now also used with matched donors. A US trial published in 2023 included 431 adults with blood cancers. All had matched or nearly matched donors and reduced-intensity treatment. At 1 year, 53% on a PTCy-based plan were alive without severe GVHD or relapse, compared with 35% on the older standard. Overall survival did not differ much between the groups.

The answer depends on the comparison. Before PTCy, half-matched transplants carried high risks. A large 2021 study of transplants reported to CIBMTR noted that PTCy had made half-matched results similar to matched unrelated donor transplants that used older GVHD prevention.

When both groups get PTCy, a well-matched unrelated donor tends to do better. A 2026 study looked at 5,873 adults with acute leukemia or myelodysplastic syndrome (MDS), reported to CIBMTR. They had transplants with PTCy from 2017 to 2021. Survival was somewhat lower with half-matched donors, with more graft failure, severe GVHD and deaths not caused by the disease. Among patients given reduced-intensity treatment, or with donors under 30, survival did not differ.

Against cord blood, a US trial ran from 2012 to 2018. It randomly assigned 368 adults aged 18 to 70 with leukemia or lymphoma to a half-matched marrow transplant or a double cord blood transplant. Its main measure, being alive at 2 years without the cancer growing, did not differ significantly. Overall survival at 2 years was higher after the half-matched transplant.

Putting this together, 2025 US guidelines generally rank a matched brother or sister first. Next comes a matched unrelated donor who can donate without too much delay. They say half-matched and partly matched unrelated donors have similar results with PTCy. Both should be considered early for patients very unlikely to find a match.

People are most likely to match a donor of similar ancestry, and some groups have fewer well-matched volunteers on registries. A 2014 model of the US registry looked at the chance of a fully matched adult unrelated donor. It ranged from 75% for white patients of European descent to 16% for Black patients of South or Central American descent.

A half-matched relative does not depend on who has joined a registry. Johns Hopkins researchers wrote in 2024 that PTCy solved the donor availability problem for the vast majority of patients who need a transplant. Among donor transplants reported to the EBMT, a European transplant group, for 2024, about 1 in 5 used a half-matched or other mismatched relative.

It has helped people with conditions other than cancer, too. NMDP lists sickle cell disease among the conditions treated this way. St. Jude Children’s Research Hospital notes that fewer than 1 in 5 people with sickle cell disease have a matched brother or sister who does not have the disease.

PTCy has also opened up more registry donors. NMDP’s Donor for All research uses it with partly matched unrelated volunteers. In its ACCESS trial, 1-year survival for adults was comparable to past results with fully matched donors. Of the people who took part, 59% came from racial and ethnic groups often underrepresented in clinical trials.

A half-match is not always possible or best. Some patients have no suitable relative, or have antibodies against the relatives they do have. US guidelines generally prefer a matched unrelated donor who can donate in time, and they link younger donors with better survival.

That is why the same guidelines recommend searching for every donor type at the same time: family members, registry volunteers and cord blood. Each volunteer who joins a registry adds another possible match, whether full or partial.

The Jada Bascom Foundation does not enroll donors or test tissue types. It helps people find the official registry where they live.