Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemia
Fanconi anemia (FA) constitutes the most common of the inherited bone marrow failure syndromes, a group of rare heterogeneous disorders characterized by cytopenia, predisposition to hematologic and solid malignancies and diverse clinical features. Currently, the only available hematopoietic curative treatment for bone marrow failure is an allogeneic hematopoietic stem cell transplantation (HSCT), although gene therapy has demonstrated evidence of efficacy and substantially reduced toxicity. It has been demonstrated that eltrombopag stimulates trilineage hematopoiesis in aplastic anemia, and preclinical studies suggest it promotes DNA repair in FA hematopoietic stem cells (HSCs). Herein, we report the experience with eltrombopag in a patient misdiagnosed with aplastic anemia and subsequently determined to have FA mosaicism and in two FA patients who previously received gene therapy but who were infused with very low numbers of gene-corrected HSCs. Strikingly, the patient with somatic mosaicism achieved transfusion independence and averted HSCT, and the gene-therapy patients showed a marked increase of corrected cells during treatment.
Authors
- Juan A. Bueren (ORCID: https://orcid.org/0000-0002-3228-7013)
- Alejandro Sanz (ORCID: https://orcid.org/0000-0001-7083-376X)
- Elena Sebastián (ORCID: https://orcid.org/0000-0002-5444-8076)
- Susana Navarro (ORCID: https://orcid.org/0000-0002-6753-546X)
- Josune Zubicaray (ORCID: https://orcid.org/0000-0003-4115-9598)
- Julián Sevilla (ORCID: https://orcid.org/0000-0002-6852-1860)
- Paula Rı́o (ORCID: https://orcid.org/0000-0002-5424-5543)
- Jean Soulier (ORCID: https://orcid.org/0000-0002-8734-5356)
- Sonsoles San Román
- June Iriondo (ORCID: https://orcid.org/0000-0001-8010-6240)
- Jose Javier Uriz
- Jonathan D. Schwartz (ORCID: https://orcid.org/0000-0002-2211-4151)
- Eileen Nicoletti
Institutions
- Centre National de la Recherche Scientifique (FR)
- Foundation for Biomedical Research (US)
- Inserm (FR)
- Université Paris Cité (FR)
- Hospital Universitario La Paz (ES)
- Assistance Publique – Hôpitaux de Paris (FR)
- Biogipuzkoa Health Research Institute (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Hôpital Saint-Louis (FR)
- Sunesis (United States) (US)
Publication Details
- Journal
- Frontiers in Pediatrics
- Published
- 2025-08-11
- DOI
- https://doi.org/10.3389/fped.2025.1625751
- Citations
- 1
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Ministerio de Ciencia, Innovación y Universidades
- European Commission
- Ministerio de Sanidad, Servicios Sociales e Igualdad
- Instituto de Salud Carlos III