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...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2025.1625751/full |
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| author | Josune Zubicaray June Iriondo Elena Sebastián Alejandro Sanz Paula Rio Jean Soulier Sonsoles San Román José J. Uriz Susana Navarro Eileen Nicoletti Juan A. Bueren Jonathan D. Schwartz Julián Sevilla |
| author_facet | Josune Zubicaray June Iriondo Elena Sebastián Alejandro Sanz Paula Rio Jean Soulier Sonsoles San Román José J. Uriz Susana Navarro Eileen Nicoletti Juan A. Bueren Jonathan D. Schwartz Julián Sevilla |
| author_sort | Josune Zubicaray |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ab05be91354941a8bb07489010eef0dd |
| institution | Kabale University |
| issn | 2296-2360 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj-art-ab05be91354941a8bb07489010eef0dd2025-08-20T04:02:27ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-08-011310.3389/fped.2025.16257511625751Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemiaJosune Zubicaray0June Iriondo1Elena Sebastián2Alejandro Sanz3Paula Rio4Jean Soulier5Sonsoles San Román6José J. Uriz7Susana Navarro8Eileen Nicoletti9Juan A. Bueren10Jonathan D. Schwartz11Julián Sevilla12Pediatric Hematology and Oncology Department and Foundation for the Biomedical Research, and Biomedical Network Research Center for Rare Diseases (CIBERER), Pediatric University Hospital Niño Jesús, Madrid, SpainPediatric Hematology and Oncology Department and Foundation for the Biomedical Research, and Biomedical Network Research Center for Rare Diseases (CIBERER), Pediatric University Hospital Niño Jesús, Madrid, SpainPediatric Hematology and Oncology Department and Foundation for the Biomedical Research, and Biomedical Network Research Center for Rare Diseases (CIBERER), Pediatric University Hospital Niño Jesús, Madrid, SpainPediatric Hematology and Oncology Department and Foundation for the Biomedical Research, and Biomedical Network Research Center for Rare Diseases (CIBERER), Pediatric University Hospital Niño Jesús, Madrid, SpainBiomedical Innovation Unit, Center for Research on Energy, Environment and Technology (CIEMAT), Biomedical Network Research Center for Rare Diseases (CIBERER) and Sanitary Research Institute Fundación Jiménez Díaz, Madrid, SpainInstitut de Recherche Saint-Louis, Inserm, CNRS, and Hôpital Saint-Louis, APHP, Université Paris Cité, Paris, FrancePediatric Hematology and Oncology Department, La Paz University Hospital, Madrid, SpainPediatric Hematology and Oncology Unit, Pediatrics Department, Donostia University Hospital, San Sebastián, SpainBiomedical Innovation Unit, Center for Research on Energy, Environment and Technology (CIEMAT), Biomedical Network Research Center for Rare Diseases (CIBERER) and Sanitary Research Institute Fundación Jiménez Díaz, Madrid, SpainRocket Pharmaceuticals, Inc., Cranbury, NJ, United StatesBiomedical Innovation Unit, Center for Research on Energy, Environment and Technology (CIEMAT), Biomedical Network Research Center for Rare Diseases (CIBERER) and Sanitary Research Institute Fundación Jiménez Díaz, Madrid, SpainRocket Pharmaceuticals, Inc., Cranbury, NJ, United StatesPediatric Hematology and Oncology Department and Foundation for the Biomedical Research, and Biomedical Network Research Center for Rare Diseases (CIBERER), Pediatric University Hospital Niño Jesús, Madrid, SpainFanconi 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.https://www.frontiersin.org/articles/10.3389/fped.2025.1625751/fullFanconi anemiabone marrow failureeltrombopaggene therapymosaicism |
| spellingShingle | Josune Zubicaray June Iriondo Elena Sebastián Alejandro Sanz Paula Rio Jean Soulier Sonsoles San Román José J. Uriz Susana Navarro Eileen Nicoletti Juan A. Bueren Jonathan D. Schwartz Julián Sevilla Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemia Frontiers in Pediatrics Fanconi anemia bone marrow failure eltrombopag gene therapy mosaicism |
| title | Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemia |
| title_full | Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemia |
| title_fullStr | Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemia |
| title_full_unstemmed | Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemia |
| title_short | Case Report: Eltrombopag in mosaic and gene therapy-treated patients with Fanconi anemia |
| title_sort | case report eltrombopag in mosaic and gene therapy treated patients with fanconi anemia |
| topic | Fanconi anemia bone marrow failure eltrombopag gene therapy mosaicism |
| url | https://www.frontiersin.org/articles/10.3389/fped.2025.1625751/full |
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