Prevalence and Risk Factors of Donor-Specific Anti-HLA Antibodies in Haploidentical Allograft Candidates: A 9698-Patient Cohort Study

When a patient needs a bone marrow transplant, doctors often turn to a relative who is not a perfect genetic match, a type of donor known as a haploidentical match. This approach has saved countless lives, but it carries a hidden obstacle: the patient's immune system may have already learned to recognize the donor's cells as foreign. This happens when the body produces specific proteins called donor-specific antibodies. Think of these antibodies as a security guard who has memorized a specific face; if that face appears, the guard sounds the alarm and attacks. In the context of a transplant, this attack can cause the new marrow to fail, leaving the patient without a cure. For years, scientists knew that pregnancy and blood transfusions could trigger this alarm, but they lacked a clear picture of how often it happened or which other factors might be to blame, especially across such a large and diverse group of patients.

To solve this puzzle, researchers at Peking University People's Hospital in Beijing embarked on a massive review of nearly ten thousand patients. Between July 2015 and December 2025, they examined the medical records of 9,698 individuals who were being evaluated for a haploidentical transplant. The team looked for the presence of those dangerous antibodies in the patients' blood and then dug deep into their histories to find the causes. They analyzed everything from the patient's age and gender to their specific blood disease, how long they had been sick, and whether they had ever been pregnant or received blood products like red blood cells or platelets. The goal was to move beyond small, limited studies and build a comprehensive map of risk that could help doctors choose the safest donors for each person.

The study revealed that about 9.6 percent of these candidates, or roughly 931 people, already carried these antibodies against their intended donors. The researchers found that the risk was not distributed evenly. Women who had been pregnant were far more likely to have these antibodies than men or women who had never been pregnant. Similarly, patients who had received blood transfusions were at a significantly higher risk. The length of time a patient had been living with their disease also mattered; those who had been sick for longer periods were more likely to have developed these antibodies. Age played a role as well, with adults and older patients showing a much higher likelihood of having antibodies compared to children.

When the researchers broke down the data by the specific type of blood disease the patients had, the picture became even more detailed. Patients with certain conditions, such as myelodysplastic syndromes and aplastic anemia, faced a higher risk of having these antibodies compared to those with acute myeloid leukemia. In contrast, patients with acute lymphoblastic leukemia had a lower risk. The study also showed that while pregnancy and transfusions were major drivers of risk across almost all groups, the influence of age and specific diseases varied depending on the patient's background. For instance, in children, the risk was driven almost entirely by whether they had received blood transfusions, whereas in adults, the underlying disease and age became more prominent factors alongside pregnancy and transfusion history.

These findings suggest that the path to a successful transplant is not just about finding a genetic match, but also about understanding the patient's unique history. The study confirms that pregnancy, blood transfusions, older age, and the specific nature of the blood disease are independent factors that can sensitize a patient's immune system. By identifying these risks, doctors can now monitor high-risk patients more closely and potentially select donors who are less likely to trigger an immune attack. The researchers noted that while their study was large and detailed, it was conducted at a single center, and future work will be needed to confirm these patterns in other hospitals and with different types of donors. Nevertheless, this massive cohort provides a solid foundation for making transplant decisions safer and more effective for thousands of patients.