Bhatt Neel S, Borogovac Azra, Efebera Yvonne A, DeSalvo Anna, Devine Steven M, Foley Amy, Greco-Stewart Valerie, Hamilton Betty K, Heuer Mykala, Molfenter Todd, Plastaras John P, Ragon Brittany K, Wall Sarah A, Broglie Larisa, Juckett Mark B, Khera Nandita, Horowitz Mary M, DeZern Amy E
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Division of Hematology, Oncology, Bone Marrow Transplant, and Cellular Therapy, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
Blood Adv. 2025 Sep 9;9(17):4448-4457. doi: 10.1182/bloodadvances.2024015405.
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.
重型再生障碍性贫血(SAA)是一种罕见且危及生命的骨髓衰竭性疾病。使用抗胸腺细胞球蛋白和环孢素的免疫抑制疗法(IST)长期以来一直是SAA的一线治疗选择;然而,其疗效持久性有限以及存在继发性恶性肿瘤等长期并发症风险仍是这种治疗方式的一个缺点。异基因造血细胞移植(HCT)是一种潜在的治愈性选择,从长期来看疗效有显著改善,尤其是对于人类白细胞抗原(HLA)匹配的相关供者。然而,此前使用替代供者,如单倍体相合、不相合或匹配的无关供者,因移植相关发病率增加,尤其是移植物抗宿主病(GVHD),而受到限制。因此,HCT一直局限于年轻受者以及有HLA匹配相关供者的患者,这给老年人以及那些没有匹配供者选择的人造成了显著差异。尽管如此,HCT领域最近的进展,如用于预防GVHD的移植后环磷酰胺,已使使用替代供者的HCT疗效得到改善;然而,替代供者HCT作为一线治疗的使用率仍然较低,部分原因是多中心试验数据有限。本综述讨论了当前SAA的治疗方法,包括IST和HCT,并强调了尚存的差距。还讨论了诸如CureAA和TransIT等正在进行的临床试验如何有助于弥补这些差距。此外,我们讨论了利益相关者参与和实施科学在将基于研究的证据整合到临床实践中的重要性。弥合这些差距对于使历史上被排除在一线HCT之外的患者,包括老年人以及种族或族裔多样化人群,能够公平获得治疗是必要的。