Excellent Outcomes in Feasibility Study of Radiation-Free Conditioning and Transplant in Pediatric 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 treated with a hematopoietic cell transplant (HCT) in the presence of an HLA HLA: See human leukocyte antigen. -matched sibling donor (MSD) with disease-free survival (DFS) of >90%. In the absence of an MSD, immunosuppressive therapy immunosuppressive therapy: Immunosuppressive drug therapy lowers your body's immune response. This prevents your immune system from attacking your bone marrow, allowing bone marrow stem cells to grow, which raises blood counts. For older patients with acquired aplastic anemia, immunosuppressive drug therapy is the… (IST) can induce remission but concerns for relapsed/refractory disease and clonal hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. persist. IST failure is an indication for HCT. Modern HCT approaches target barriers such as graft rejection (GR), 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… , and transplant-related toxicities. Traditionally, total body irradiation (TBI) inclusive HCT conditioning helps decrease GR, but the use of TBI in children increases concerns for late effects such as malignancies. To describe outcomes after HCT in children with SAA transplanted from the best available donor following a radiation-free RIC regimen in a single-center feasibility trial. The RIC regimen included alemtuzumab alemtuzumab: Alemtuzumab is a drug used in the treatment of chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL) and T-cell lymphoma under the trade names Campath, MabCampath and Campath-1H, and in the treatment of multiple sclerosis as Lemtrada. It is also used in some conditioning regimens for… , fludarabine fludarabine: The U.S. Food and Drug Administration (FDA) approved fludarabine for treating chronic lymphocytic leukemia (CCL). Researchers are studying fludarabine in combination with other medicines for treating bone marrow failure. , melphalan, ±thiotepa prior to HCT GVHD prophylaxis included 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… , methotrexate, or 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… . Abatacept was added to GVHD prophylaxis after 2017 to decrease further or eliminate GVHD risk in patients with a non-malignant disorder. This report includes outcomes in 22 consecutive pediatric SAA recipients of HCT (11 MSD, 10 unrelated, and 1 haploidentical) between 2012 and 2023 at a single center. With a median follow-up of 48 months (range, 12-144) all recipients had sustained full myeloid donor chimerism, 100% DFS, and no grade 2 to 4 acute GVHD. One patient (4.5%) developed grade 1 acute skin GVHD, and 1 (4.5%) developed pericardial effusion attributed to chronic GVHD. Complications before day +180 were primarily transient viral reactivations. Thyroid and ovarian hypofunction were the commonest effects noted at long-term follow-up. This radiation-free RIC regimen demonstrated excellent DFS with minimal GVHD in all patients, including those from alternative donor sources. Late complications were primarily endocrine in origin.