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Large-scale expansion and transplantation of CD34+ hematopoietic cells: in vitro and in vivo confirmation of neutropenia abrogation related to the expansion process without impairment of the long-term engraftment capacity

Authors

  • Jean-Michel Boiron,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Bernard Dazey,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Christian Cailliot,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Béatrice Launay,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Michel Attal,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Frédéric Mazurier,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Ian K. McNiece,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Zoran Ivanovic,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Jean Caraux,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Gérald Marit,

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Josy Reiffers

    1. From CHU Bordeaux, Pessac, France; Victor Segalen University, Bordeaux 2, France; the Department of Cell Therapy, French Blood Establishment Aquitaine-Limousin (EFSAL); Hospital University Center, Toulouse, France; INSERM EO 217, Victor Segalen University, Bordeaux 2, France; Amgen Inc. Thousand Oaks, California; the Johns Hopkins Oncology Center, Division of Hematologic Malignancies, Baltimore, Maryland; and Amgen SA, Neuilly sur-Seine, France.
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  • Supported by grants, cytokines, and culture medium from Amgen Inc. (Thousand Oaks, CA) and Amgen SA (Neuilly sur-Seine, France) and the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2000).

JM Boiron, Etablissement Français du Sang Aquitaine = Limousin, Place A Raba Léon, 33035 Bordeaux; e-mail: jean-michel.bciron@efs.sante.fr.

Abstract

BACKGROUND: Herein are reported the results obtained in all multiple myeloma patients transplanted with peripheral blood hematopoietic progenitor cells submitted to ex vivo expansion.

STUDY DESIGN AND METHODS: Patients had blood progenitor cell mobilization with cyclophosphamide and filgrastim. CD34+ cells were expanded for 10 days in a medium containing granulocyte–colony-stimulating factor (G-CSF), stem cell factor, and megakaryocyte growth and development factor (MGDF). Twenty-seven patients underwent transplantation with expanded and nonexpanded cells and 7 patients underwent transplantation with expanded cells only.

RESULTS: The median fold cell expansion was 29.1. The number of colony-forming unit–granulocyte-macrophage (CFU-GM) and CD34+ cells, and the long-term culture-initiating cell (LTC-IC) activity increased with median fold values of 14.7, 2.75, and 2.25, respectively. Postmyeloablative neutropenia was abrogated in 24 of 27 patients transplanted with expanded cells plus nonexpanded cells. The median duration of severe neutropenia was 0 days and correlated with the number of cells and CFU-GM infused. Survival was similar to that of a historical control group. Our LTC-IC and NOD-SCID mice studies showed that the expanded cells are able of sustaining long-term hematopoiesis. Seven other patients received transplantation with expanded cells alone. Absolute neutropenia was abrogated in 6 patients. The median duration of neutropenia was 0 days. Two patients who received the lower number of total cells or CFU-GM had brief secondary neutropenia, which resolved after G-CSF injections.

CONCLUSION: CD34+ cells expanded ex vivo can abrogate absolute and severe neutropenia after high-dose therapy. The results of the amplification process are strongly related to the delay of hematopoietic recovery.

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