People who have elevated levels of donor-specific anti-HLA antibodies (DSAs) — immune system proteins that can target and attack donor stem cells — wait an average of three additional months to receive blood or bone marrow transplants from a healthy donor, according to recent research from investigators at the Johns Hopkins Kimmel Cancer Center. Those most likely to be affected are Black women who have had prior pregnancies, researchers found, in work supported by the National Institutes of Health.
High levels of DSAs have been associated with graft failure and other negative outcomes, says lead study author Christian Gocke, M.D., Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine.
"DSAs are really one of the key determinants in whether the donor search goes smoothly," Gocke says. "They can sometimes change over time and shoot up at the last minute, making the process of finding a compatible donor more complicated." The study was published online Nov. 7, 2025, in the journal Transplantation and Cellular Therapy.
About half of patients can be helped through a desensitization protocol developed at Johns Hopkins that increases the odds of a patient being able to successfully accept a transplant from a donor, Gocke says. The plan includes total body irradiation; plasma exchange, a process in which blood plasma containing antibodies is removed from the blood and replaced with normal antibody; and anti-rejection medications.
For the study, Gocke and colleagues reviewed records from 2014–2022 of 408 patients undergoing donor blood or bone marrow transplant who had at least one antibody against any potential donor. Maria Bettinotti, Ph.D., senior study author and director of the Immunogenetics Laboratory at Johns Hopkins, and her colleagues at the laboratory played a key role in providing the DSA laboratory data behind this analysis.
Armed with this data, they looked first at the impact of antibodies on donor screening and time to transplant, and then at transplant outcomes, by comparing 208 patients who had DSAs (71 who underwent the desensitization protocol and 137 who did not) and an additional 200 who had an antibody against a potential donor but not the donor from whom they ultimately received a transplant.
Patients with elevated anti-HLA antibodies experienced significantly prolonged time to transplant — a median of 120 days compared with a median of 90 days for patients who did not have elevated antibodies. This increased for minority patients who required a non-relative donor (average of 219 days to transplant).
Those with high antibodies also required more potential donors be evaluated (average of four versus two for those without high antibodies). Minorities overall were less likely to receive a transplant from an unrelated donor and more likely to receive a suboptimal related donor transplant. The desensitization protocol reduced antibody levels to a point where patients had comparable outcomes to those with low-level antibodies, including similar graft failure and engraftment rates. However, the current desensitization protocols are not sufficient, Gocke says.
He is now principal investigator of a new clinical trial testing the drug Darzalex Faspro, typically used for multiple myeloma, to kill antibody-making cells before the desensitization protocol.
Study co-authors were Marianna Zahurak, Ilias Sinanidis, Suraya Berger, Javier Bolaños-Meade, Ephraim Fuchs, Alexander Ambinder, Philip Imus, Amy DeZern, Richard Jones and Ravi Varadhan. The work was supported by the National Institutes of Health, National Cancer Institute grant P01 CA2259.
