The use of reduced-intensity conditioning HLA-haploidentical bone marrow transplant (BMT) and posttransplantation cyclophosphamide (PTCy)-based prophylaxis for graft vs host disease (GVHD) for the treatment of severe aplastic anemia (SAA) among patients without a fully matched donor resulted in high rates of survival and low rates of acute and chronic GVHD, according to the results from a phase 2 trial. The data were published in the journal Blood.

The cohort in the trial comprised 35% of patients from underrepresented racial and/or ethnic groups, demonstrating that this BMT approach for patients without a fully matched donor not only improves outcomes, but also expands access to BMT.

The single-arm, phase 2 trial ( identifier: NCT02833805) treated 27 patients with SAA who lacked a fully matched donor by reduced-intensity conditioning followed by an HLA-haploidentical BMT and then PTCy-based GVHD prophylaxis. During conditioning, a total body irradiation dose was 200 cGy among the first 7 patients, but was increased to 400 cGy to the remaining 20 patients.

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The primary endpoint of the trial was feasibility and safety. Secondary endpoints included 1-year OS, rates of grade 2 and 4 acute or chronic GVHD, and graft failure.

The median age of the entire cohort was 25 and 48% of patients were female. There were 63% of patients who were non-Hispanic White, 19% who were non-Hispanic Black, 3% who were Hispanic Black, 11% who were Asian/Pacific Islander, and 3% who reported more than 1 race. A very severe diagnosis was present for 52% of patients and clonality was present at baseline among 81%.

At day 100, the cumulative rate of grade 2 or 4 acute GVHD was 7%. At 2 years, the rate of chronic GVHD was 4%.

Infections were common, affecting 67% of patients; however, the majority were grade 2 in severity. There were 2 patients who died as a result of an infection. The most common etiology was viral, followed by bacterial and fungal. The incidence of cytomegalovirus infection was 40.7%, of which, 54.5% required treatment.

Neutrophil recovery was achieved by day 28 among 26 patients, with a median time to recovery of 17 days. The 100-day incidence of platelet recovery was 88%, with a median time to platelet recovery of 25.5 days.

The OS of the entire cohort was 92% at 1 year and was sustained through year 3. Among the 20 patients who received the higher dose of irradiation, the OS rate was 100%. The lower irradiation dose was also associated with an increased risk of graft failure, which affected 3 patients compared with none of the patients in the higher dose cohort (P =.01).

“Not only does this approach avoid any adverse ramifications of immunosuppressive therapy and its low failure-free survival, but he use of haploidentical donors also expands access to BMT across all populations,” the authors concluded in their report.

DeZern AE, Zahurak M, Symons HJ, et al. Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. Blood. 2023;141:3031-3038. doi:10.1182/blood.2023020435