Researchers at the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health in Bethesda, Maryland, have proposed a new method for increasing the efficacy of peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (HSCT) in patients with severe aplastic anemia (SAA). They presented their findings at the 64th American Society of Hematology Annual Meeting and Exposition.
Grafts from PBSCs typically achieve high rates of engraftment, but they also carry high risk of graft-versus-host disease (GVHD). To address the prevalence of GVHD with this type of transplant, Georg Aue, MD, PhD, MBA, and his associates at the NHLBI have proposed using a bone marrow transplant-equivalent dose of T cells in tandem with the PBSC HSCT.
All patients enrolled in this phase II trial (n=35; median age, 30 years) had a diagnosis of SAA or other bone marrow failure syndrome. All patients underwent the same pretransplant immunosuppression with cyclophosphamide, antithymocyte globulin, and fludarabine. Patients who received matched unrelated donor (MUD) transplants underwent small-dose total body irradiation in addition to the therapeutic immunosuppressors.
For the transplant, patients were given both CD34+ granulocyte colony-stimulating factor (GCSF) stem cells (median dose, 8×106) and CD3+ T cells (collected from the same donor prior to GCSF mobilization; median dose, 2×107).
All patients received GVHD prophylaxis with cyclosporin and methotrexate.
The primary study outcome was incidence of chronic GVHD at 1-year posttransplant, which was 11% in this cohort.
Secondary outcomes included mortality, engraftment and chimerism, acute GVHD, immune reconstitution, and matched related (MRD) versus MUD. At a median follow-up of 5 years, overall survival was 85%. A total of 94% of patients achieved engraftment, and most patients achieved >95% donor myeloid (97%) and T-cell (94%) chimerism. Grade II-IV GVHD had an incidence of 23%. Most patients achieved full immune reconstitution by 1 year posttransplant, though this abstract did not provide a percentage. Aside from having a slower time to neutrophil recovery and slightly higher graft failure incidence, patients who received transplants from MUDs fared similarly to those who received transplants from MRDs.
“For patients with SAA and other [bone marrow failure] syndromes, transplanting high doses of mobilized CD34+ selected cells from MRD and MUD donors combined with a bone marrow transplant equivalent of nonmobilized donor T cells (a partially T-cell-depleted PBSC transplant) achieves rapid and durable donor engraftment and excellent survival,” the researchers wrote. They noted that acute and chronic GVHD incidence was significantly lower in their cohort than in reports of conventional PBSC HSCTs.
Aue G, Migdady Y, Wang Y, et al. Allogeneic peripheral blood stem cell transplantation for bone marrow failure syndromes using CD34+-selected progenitor cells co-infused with a reduced number of non-mobilized T-cells. Abstract #3372. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.