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Review
. 2025 Sep 9;9(17):4448-4457.
doi: 10.1182/bloodadvances.2024015405.

Up-front alternative donor HCT in severe aplastic anemia: gaps and opportunities to translate evidence into practice

Neel S Bhatt  1   2 , Azra Borogovac  3 , Yvonne A Efebera  4 , Anna DeSalvo  5 , Steven M Devine  5 , Amy Foley  5 , Valerie Greco-Stewart  5 , Betty K Hamilton  6 , Mykala Heuer  5 , Todd Molfenter  7 , John P Plastaras  8 , Brittany K Ragon  9 , Sarah A Wall  10 , Larisa Broglie  11   12 , Mark B Juckett  13 , Nandita Khera  14 , Mary M Horowitz  12 , Amy E DeZern  15
Affiliations
Review

Up-front alternative donor HCT in severe aplastic anemia: gaps and opportunities to translate evidence into practice

Neel S Bhatt et al. Blood Adv. .

Abstract

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.

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Conflict of interest statement

Conflict-of-interest disclosure: A.E.D. reports advisory board fees and/or consultancy fees and honoraria from Bristol Myers Squibb, Agios, and Novartis; and serving on clinical trial committees or data safety monitoring boards for Novartis, AbbVie, Kura, Geron, Servier, Keros, Shattuck Labs, and Bristol Myers Squibb. M.M.H. reports research funding from Sobi and Incyte. N.K. reports consulting fees from Incyte. A.B. reports speakers’ bureau and advisory board fees from Janssen. B.H. reports ad hoc advisory board fees from Sanofi, Incyte, Rigel, and MaaT Pharma; consultancy fees from ACI Group; data safety monitoring committee fees from Angiocrine; and adjudication committee fees from CSL Behring. B.R. reports advisory board fees from Astellas, Pfizer, Genentech, and Syndax. S.W. reports education bureau speaker fees from Sobi; advisory board participation (completed 11 December 2023) for MorphoSys; and research support for conducting clinical trials as site principal investigator from CTI Biopharma, Incyte, Telios, and AbbVie. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Current treatment paradigm in patients diagnosed with SAA: standard of care and gaps in knowledge. MSD, matched sibling donor.
Figure 2.
Figure 2.
Stakeholder awareness and engagement to improve dissemination and implementation of trials assessing the role of up-front alternative donor HCT in patients with SAA.
See this image and copyright information in PMC

References

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    1. Burroughs LM, Woolfrey AE, Storer BE, et al. Success of allogeneic marrow transplantation for children with severe aplastic anaemia. Br J Haematol. 2012;158(1):120–128. - PMC - PubMed

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