Half-Matched Family Donors Could Expand Transplant Access for Severe Aplastic Anemia

Severe aplastic anemia is a rare, life-threatening disorder in which the bone marrow fails to produce enough healthy blood cells, leaving children and young adults vulnerable to anemia, infection, and bleeding. Curative treatment often requires bone marrow transplantation, but many patients lack a fully matched sibling and may face difficulty finding a suitable unrelated donor. To expand access to transplantation, researchers have developed a half-matched donor approach that may offer a curative option to more patients.

The approach was developed at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD, USA) and evaluated with the Johns Hopkins Children’s Center. It uses haploidentical, or half-matched, family donors such as parents, siblings, or other relatives. Patients receive reduced-intensity conditioning with lower doses of chemotherapy and radiation before transplantation.

The method also includes cyclophosphamide after transplantation to help prevent graft-versus-host disease. This complication occurs when donor immune cells attack the recipient’s healthy organs and tissues. By using family donors who are readily available, the strategy addresses a major barrier in timely transplant access.

The retrospective review included 31 patients ages 2 to 20 who underwent bone marrow transplantation at Johns Hopkins between 2014 and 2024. Twenty-three patients received the reduced-intensity platform with posttransplant cyclophosphamide, including 21 who received marrow from half-matched family donors and two from fully matched siblings. Eight patients received standard-of-care matched-sibling transplants with a different drug regimen before and after transplantation.

Among the 23 patients treated with posttransplant cyclophosphamide, 22 survived, yielding an overall survival rate of 96%. All 14 patients whose disease had returned or had not fully responded to previous therapy survived, as did eight of nine patients who had not received prior treatment. All eight patients who received standard-of-care matched-sibling transplants also survived.

The findings were published August 3 in Blood Advances. At one year, surviving patients who received the newer approach had at least 95% donor-derived blood cells, indicating durable engraftment. All surviving patients remained independent of blood transfusions at last follow-up, serious graft-versus-host disease was uncommon, and 95% no longer required immune-suppressing medications one year after transplantation.

The investigators noted that long-term complications were generally infrequent, although some patients had kidney problems or changes in reproductive hormone function. They also cautioned that the study was relatively small and that longer follow-up is needed to assess late effects.

“These findings show that we can overcome longstanding barriers to donor availability while achieving durable engraftment and excellent survival,” said Margarita Dionysiou, M.D., pediatric oncologist and first author on the study. “For children and young adults with severe aplastic anemia, this approach offers an opportunity for a cure without the delays associated with searching for a fully matched donor.”

Related Links
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins Children’s Center