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Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes

Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and...

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Autores principales: Sevilla, Julián, Navarro, Susana, Rio, Paula, Sánchez-Domínguez, Rebeca, Zubicaray, Josune, Gálvez, Eva, Merino, Eva, Sebastián, Elena, Azqueta, Carmen, Casado, José A., Segovia, José C., Alberquilla, Omaira, Bogliolo, Massimo, Román-Rodríguez, Francisco J., Giménez, Yari, Larcher, Lise, Salgado, Rocío, Pujol, Roser M., Hladun, Raquel, Castillo, Ana, Soulier, Jean, Querol, Sergi, Fernández, Jesús, Schwartz, Jonathan, García de Andoín, Nagore, López, Ricardo, Catalá, Albert, Surralles, Jordi, Díaz-de-Heredia, Cristina, Bueren, Juan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390450/
https://www.ncbi.nlm.nih.gov/pubmed/34485595
http://dx.doi.org/10.1016/j.omtm.2021.06.001
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author Sevilla, Julián
Navarro, Susana
Rio, Paula
Sánchez-Domínguez, Rebeca
Zubicaray, Josune
Gálvez, Eva
Merino, Eva
Sebastián, Elena
Azqueta, Carmen
Casado, José A.
Segovia, José C.
Alberquilla, Omaira
Bogliolo, Massimo
Román-Rodríguez, Francisco J.
Giménez, Yari
Larcher, Lise
Salgado, Rocío
Pujol, Roser M.
Hladun, Raquel
Castillo, Ana
Soulier, Jean
Querol, Sergi
Fernández, Jesús
Schwartz, Jonathan
García de Andoín, Nagore
López, Ricardo
Catalá, Albert
Surralles, Jordi
Díaz-de-Heredia, Cristina
Bueren, Juan A.
author_facet Sevilla, Julián
Navarro, Susana
Rio, Paula
Sánchez-Domínguez, Rebeca
Zubicaray, Josune
Gálvez, Eva
Merino, Eva
Sebastián, Elena
Azqueta, Carmen
Casado, José A.
Segovia, José C.
Alberquilla, Omaira
Bogliolo, Massimo
Román-Rodríguez, Francisco J.
Giménez, Yari
Larcher, Lise
Salgado, Rocío
Pujol, Roser M.
Hladun, Raquel
Castillo, Ana
Soulier, Jean
Querol, Sergi
Fernández, Jesús
Schwartz, Jonathan
García de Andoín, Nagore
López, Ricardo
Catalá, Albert
Surralles, Jordi
Díaz-de-Heredia, Cristina
Bueren, Juan A.
author_sort Sevilla, Julián
collection PubMed
description Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34(+) cells/μL required to initiate apheresis. A median of 21.8 CD34(+) cells/μL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34(+) cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34(+) cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34(+) cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34(+) cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols.
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spelling pubmed-83904502021-09-03 Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes Sevilla, Julián Navarro, Susana Rio, Paula Sánchez-Domínguez, Rebeca Zubicaray, Josune Gálvez, Eva Merino, Eva Sebastián, Elena Azqueta, Carmen Casado, José A. Segovia, José C. Alberquilla, Omaira Bogliolo, Massimo Román-Rodríguez, Francisco J. Giménez, Yari Larcher, Lise Salgado, Rocío Pujol, Roser M. Hladun, Raquel Castillo, Ana Soulier, Jean Querol, Sergi Fernández, Jesús Schwartz, Jonathan García de Andoín, Nagore López, Ricardo Catalá, Albert Surralles, Jordi Díaz-de-Heredia, Cristina Bueren, Juan A. Mol Ther Methods Clin Dev Original Article Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34(+) cells/μL required to initiate apheresis. A median of 21.8 CD34(+) cells/μL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34(+) cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34(+) cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34(+) cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34(+) cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols. American Society of Gene & Cell Therapy 2021-06-12 /pmc/articles/PMC8390450/ /pubmed/34485595 http://dx.doi.org/10.1016/j.omtm.2021.06.001 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Sevilla, Julián
Navarro, Susana
Rio, Paula
Sánchez-Domínguez, Rebeca
Zubicaray, Josune
Gálvez, Eva
Merino, Eva
Sebastián, Elena
Azqueta, Carmen
Casado, José A.
Segovia, José C.
Alberquilla, Omaira
Bogliolo, Massimo
Román-Rodríguez, Francisco J.
Giménez, Yari
Larcher, Lise
Salgado, Rocío
Pujol, Roser M.
Hladun, Raquel
Castillo, Ana
Soulier, Jean
Querol, Sergi
Fernández, Jesús
Schwartz, Jonathan
García de Andoín, Nagore
López, Ricardo
Catalá, Albert
Surralles, Jordi
Díaz-de-Heredia, Cristina
Bueren, Juan A.
Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes
title Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes
title_full Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes
title_fullStr Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes
title_full_unstemmed Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes
title_short Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes
title_sort improved collection of hematopoietic stem cells and progenitors from fanconi anemia patients for gene therapy purposes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390450/
https://www.ncbi.nlm.nih.gov/pubmed/34485595
http://dx.doi.org/10.1016/j.omtm.2021.06.001
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