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

2021; Cell Press; Volume: 22; Linguagem: Inglês

10.1016/j.omtm.2021.06.001

2329-0501

Julián Sevilla, Susana Navarro, Paula Rı́o, Rebeca Sánchez‐Domínguez, Josune Zubicaray, Eva Heredero Gálvez, Eva Merino, Elena Sebastián, Carmen Azqueta, José Antonio Casado, José C. Segovia, Omaira Alberquilla, Massimo Bogliolo, Francisco J Roman‐Rodriguez, Yari Giménez, Lise Larcher, Rocío Salgado, Roser Pujol, Raquel Hladun, Ana Pérez Castillo, Jean Soulier, Sergi Querol, Jesús Fernández‐Sojo, Jonathan D. Schwartz, Nagore García de Andoín, Ricardo López Almaraz, Albert Catalá, Jordi Surrallés, Cristina Díaz de Heredia, Juan A. Bueren,

DNA Repair Mechanisms

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/mL required to initiate apheresis.A median of 21.8 CD34 + cells/mL 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.