Up-front alternative donor HCT in severe aplastic anemia: gaps and opportunities to translate evidence into practice. Blood Adv 2025 Sep 09;9(17):4448-4457
Date
06/24/2025Pubmed ID
40554428Pubmed Central ID
PMC12410533DOI
10.1182/bloodadvances.2024015405Scopus ID
2-s2.0-105014911723 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure disorder. Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine has long been a frontline treatment option in SAA; however, its limited durability and risk of long-term complications such as secondary malignancies remain a drawback in this treatment modality. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, particularly with HLA-matched related donors. However, the use of alternative donors, such as haploidentical, mismatched, or matched unrelated donors, has previously been limited due to increased transplant-related morbidity, particularly graft-versus-host disease (GVHD). HCTs have therefore been limited to young recipients and those with HLA-matched related donors, creating significant disparity for older adults and those who lack matched donor options. Nevertheless, more recent advances in HCT, such as posttransplant cyclophosphamide for GVHD prophylaxis, have led to improved outcomes of HCT with alternative donors; however, alternative donor HCT remains underused as up-front therapy, in part because of limited multicenter trial data. This review discusses current SAA treatment approaches, including both IST and HCT, and highlights remaining gaps. It also discusses how ongoing clinical trials such as CureAA and TransIT could help address these gaps. Furthermore, we discuss the importance of stakeholder engagement and implementation science in the integration of research-based evidence into clinical practice. Bridging these gaps is necessary for achieving equitable access for patients historically excluded from frontline HCT, including older adults and racially or ethnically diverse populations.
Author List
Bhatt NS, Borogovac A, Efebera YA, DeSalvo A, Devine SM, Foley A, Greco-Stewart V, Hamilton BK, Heuer M, Molfenter T, Plastaras JP, Ragon BK, Wall SA, Broglie L, Juckett MB, Khera N, Horowitz MM, DeZern AEAuthors
Larisa Broglie MD, MS Associate Professor in the Pediatrics department at Medical College of WisconsinMary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Anemia, AplasticGraft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Tissue Donors
Transplantation Conditioning
Transplantation, Homologous
Treatment Outcome
Unrelated Donors
