Hematopoietic stem cell mobilization for gene therapy: superior mobilization by the combination of granulocyte-colony stimulating factor plus plerixafor in patients with β-thalassemia major
| Autor: | Asimina Bouinta, Evangelia Yannaki, Erica C. Jonlin, Garyfalia Karponi, Varnavas Constantinou, Achilles Anagnostopoulos, Varvara Tachynopoulou, Fani Zervou, George Stamatoyannopoulos, Konstantina Kotta, Thalia Papayannopoulou |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Benzylamines Genetic enhancement CD34 Antigens CD34 Pharmacology Biology Cyclams Colony-Forming Units Assay Young Adult Heterocyclic Compounds Granulocyte Colony-Stimulating Factor Genetics medicine Humans Molecular Biology Hematopoietic Stem Cell Mobilization Research Articles Mobilization Plerixafor beta-Thalassemia Hematopoietic Stem Cell Transplantation Genetic Therapy Hematopoietic Stem Cells Combined Modality Therapy Granulocyte colony-stimulating factor Haematopoiesis Phenotype Treatment Outcome Immunology Molecular Medicine Female Stem cell medicine.drug |
| Zdroj: | Human gene therapy. 24(10) |
| ISSN: | 1557-7422 |
| Popis: | Successful stem cell gene therapy requires high numbers of genetically engineered hematopoietic stem cells collected using optimal mobilization strategies. Here we focus on stem cell mobilization strategies for thalassemia and present the results of a plerixafor-based mobilization trial with emphasis on the remobilization with granulocyte-colony stimulating factor (G-CSF)+plerixafor in those patients who had previously failed mobilization. Plerixafor rapidly mobilized CD34(+) cells without inducing hyperleukocytosis; however, 35% of patients failed to reach the target cell dose of ≥6×10(6) CD34(+) cells/kg. Four subjects who failed on either plerixafor or G-CSF were remobilized with G-CSF+plerixafor. The combination proved highly synergistic; the target cell dose was readily reached and the per-apheresis yield was significantly increased over initial mobilization, ultimately resulting in single-apheresis collections, despite a more than 50% reduction of the dose of G-CSF in splenectomized patients to avoid hyperleukocytosis. The total stem and progenitor cells mobilized in G-CSF+plerixafor patients were higher than in patients treated by plerixafor alone. Importantly, the G-CSF+plerixafor-mobilized cells displayed a primitive stem cell phenotype and higher clonogenic capacity over plerixafor-mobilized cells. G-CSF+plerixafor represents the optimal strategy when very high yields of stem cells or a single apheresis is required. The high yields and the favorable transplantation features render the G-CSF+plerixafor-mobilized cells the optimal CD34(+) cell source for stem cell gene therapy applications. |
| Databáze: | OpenAIRE |
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