Half-matched transplants show high survival in severe aplastic anemia

A retrospective cohort study at Johns Hopkins found that 22 of 23 children, adolescents and young adults with severe aplastic anemia who received a reduced-intensity bone marrow transplant regimen with post-transplant cyclophosphamide were alive, yielding an overall survival rate of 96%. The series included 31 patients treated between 2014 and 2024. Among the 23 patients receiving the reduced-intensity regimen, 21 received bone marrow from a half-matched family donor and two from fully matched siblings; eight other patients underwent standard-of-care transplants from matched siblings using a different combination of drugs.

Severe aplastic anemia is a rare, life-threatening disorder in which the bone marrow fails to produce enough healthy blood cells. The shortages can affect red blood cells that carry oxygen, white blood cells that fight infection and platelets that help blood clot. Bone marrow transplantation can potentially cure the disorder by replacing damaged blood-forming cells with healthy donor cells, but its use depends on finding a suitable donor. The researchers noted that only about 25% to 30% of patients have a fully matched sibling donor, while finding an unrelated matched donor can be especially difficult for patients from racial and ethnic minority populations who are underrepresented in donor registries.

The Johns Hopkins approach used haploidentical, or half-matched, donors such as parents, siblings and other relatives, expanding the potential donor pool. Patients received reduced-intensity conditioning, involving lower doses of chemotherapy and radiation therapy to prepare for transplantation, and then received cyclophosphamide after the procedure to help prevent graft-versus-host disease. In that potentially serious complication, donor immune cells attack the recipient’s healthy organs and tissues. Of the 23 patients treated with the reduced-intensity approach, all 14 whose disease had returned or failed to respond to previous treatment survived. Eight of the nine patients who had not received previous treatment also survived. All eight patients receiving standard-of-care matched-sibling transplants were alive.

Donor cells established themselves and continued producing healthy blood cells in nearly all patients receiving the newer approach. At one year, surviving patients had at least 95% donor-derived blood cells, indicating strong engraftment. All surviving patients were independent of blood transfusions at their last follow-up. Serious graft-versus-host disease was uncommon, and 95% of surviving patients no longer required medications to suppress their immune systems one year after transplantation. Long-term complications were generally infrequent, although some patients experienced kidney problems or changes in reproductive hormone function. The investigators said the results support the feasibility of using readily available family donors while maintaining high survival and low rates of serious complications in this young patient population.

The findings offer a potential option for young patients with severe aplastic anemia who lack a fully matched donor, including those whose disease has returned or has not completely responded to initial therapy and those who have not previously received treatment. The results build on earlier work at the Kimmel Comprehensive Cancer Center using cyclophosphamide to manage graft-versus-host disease and half-matched transplantation. However, the study was relatively small and limited to one center, and the donor composition and treatment regimens differed between the groups: two of the 23 reduced-intensity-group patients received marrow from fully matched siblings, while the eight-patient comparison group received a different regimen from matched siblings. The researchers cautioned that longer follow-up is needed to assess potential late effects fully.

Subject of Research: Reduced-intensity bone marrow transplantation with post-transplant cyclophosphamide for severe aplastic anemia in children and young adults

Article Title: Half-matched bone marrow transplant expands treatment options for children and young adults with severe aplastic anemia

Article References: Half-matched bone marrow transplant expands treatment options for children and young adults with severe aplastic anemia. Original publication (Bibliographic details unavailable.)

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Keywords: severe aplastic anemia, bone marrow transplantation, haploidentical donors, post-transplant cyclophosphamide, pediatric oncology, graft-versus-host disease, donor engraftment, overall survival, retrospective cohort, Half-matched, bone, marrow