PTCy-based allo-BMT platform as a curative, accessible alternative for pediatric and young adult severe aplastic anemia

Severe aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… (SAA) is a life-threatening bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… syndrome. Allogeneic bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. transplantation (allo-BMT) is the most definitive curative treatment for SAA and is prioritized when matched sibling donors (MSDs) are available. Haploidentical BMT (haplo-BMT) with posttransplant cyclophosphamide cyclophosphamide: Cyclophosphamide is in a class of medications called alkylating agents. When used to treat cancer, it works by slowing or stopping the growth of cancer cells in your body. When cyclophosphamide is used to treat bone marrow failure, it works by suppressing your body's immune system. (PTCy) has emerged as a promising alternative, expanding donor access while mitigating historically high rates of graft failure and graft-versus-host disease (GVHD) graft-versus-host disease (GVHD): Also called GVHD, it is a common complication of bone marrow/stem cell transplantation. It is caused when the donor's immune cells, now in the patient, begin to see the the patient's body as foreign and mount an immune response. GVHD most commonly effects the recipient's skin, intestines, or liver… . We report the outcomes of 31 consecutive pediatric, adolescent, and young adult patients (aged ≤21 years) with acquired SAA who underwent allo-BMT at a single institution (2014-2024). Patients with treatment-naïve (TN) and relapsed/refractory (R/R) SAA were included. Patients received reduced-intensity conditioning (RIC) haplo-BMT or MSD-BMT with PTCy, mycophenolate mofetil mycophenolate mofetil: Mycophenolate mofetil is approved by the U.S. Food and Drug Administration (FDA) to prevent organ rejection in people who have received a kidney, heart, or liver transplant. This medicine comes as a capsule, tablet, or liquid that is taken by mouth. Researchers are currently studying MMF in… , and tacrolimus tacrolimus: Tacrolimus is in a class of medications called immunosuppressants. It works by decreasing the activity of the immune system. Tacrolimus can be prescribed to treat and prevent graft vs host disease (GVHD). It can also be used as part of combination therapy to treat aplastic anemia in place of… (PTCy cohort, n = 23), or standard-of-care (SOC) MSD-BMT with cyclophosphamide/antithymocyte globulin conditioning and calcineurin inhibitor/methotrexate-based GVHD prophylaxis (SOC cohort, n = 8). Overall survival was 97% (PTCy, 96%; SOC, 100%). GVHD rates were low, with only 1 case of grade 2 acute GVHD and 1 case of extensive chronic GVHD (cGVHD) in the PTCy group, and 1 case of extensive cGVHD in the SOC group. No patients developed clonal hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. . Late effects were infrequent, and limited to menstrual dysfunction and BK virus-associated nephropathy in 1 patient. Robust donor chimerism was achieved in the PTCy cohort, in contrast to uniformly mixed chimerism in the SOC group. These findings demonstrate that RIC haplo-BMT with PTCy is a safe and effective curative approach for pediatric patients with both R/R and TN SAA, supporting its use as a frontline option even when MSDs are available.