Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
Alessandra Magnani,
Corinne Pondarré,
Naïm Bouazza,
Jeremy Magalon,
Annarita Miccio,
Emmanuelle Six,
Cecile Roudaut,
Cécile Arnaud,
Annie Kamdem,
Fabien Touzot,
Aurélie Gabrion,
Elisa Magrin,
Chloé Couzin,
Mathieu Fusaro,
Isabelle André,
Jean-Paul Vernant,
Eliane Gluckman,
Françoise Bernaudin,
Dominique Bories,
Marina Cavazzana
Affiliations
Alessandra Magnani
Department of Biotherapy, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM CIC 1416, Paris, France
Corinne Pondarré
Centre de référence de drépanocytose, CHIC Centre Hospitalier Intercommunal de Créteil, Créteil, France;Inserm U955, Paris XII University, Créteil, France
Naïm Bouazza
Université Paris Descartes, EA7323, Sorbonne Paris Cité, CIC-1419 Inserm, Cochin-Necker, Paris, France
Jeremy Magalon
Cell Therapy Unit, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
Annarita Miccio
Laboratory of Chromatin and gene regulation during development, Imagine Institute, Paris, France;Paris Descartes–Sorbonne Paris Cité University, Imagine Institute, Paris
Emmanuelle Six
Paris Descartes–Sorbonne Paris Cité University, Imagine Institute, Paris;Human Lymphohematopoiesis Laboratory, Inserm UMR 1163, Imagine Institute, University Paris Descartes Sorbonne Paris Cité, Paris, France
Cecile Roudaut
Department of Biotherapy, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
Cécile Arnaud
Centre de référence de drépanocytose, CHIC Centre Hospitalier Intercommunal de Créteil, Créteil, France
Annie Kamdem
Centre de référence de drépanocytose, CHIC Centre Hospitalier Intercommunal de Créteil, Créteil, France
Fabien Touzot
Department of Immunology-Allergy-Rheumatology, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada
Aurélie Gabrion
Department of Biotherapy, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
Elisa Magrin
Department of Biotherapy, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM CIC 1416, Paris, France
Chloé Couzin
Department of Biotherapy, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
Mathieu Fusaro
Study Center for Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker-Enfants Malades University Hospital, Paris, France
Isabelle André
Paris Descartes–Sorbonne Paris Cité University, Imagine Institute, Paris;Human Lymphohematopoiesis Laboratory, Inserm UMR 1163, Imagine Institute, University Paris Descartes Sorbonne Paris Cité, Paris, France
Jean-Paul Vernant
Hematology Department, Pitié-Salpêtrière Hospital, Paris, France
Eliane Gluckman
Monacord Hôpital Saint Louis Paris, Centre Scientifique de Monaco, Monaco and Eurocord, Hôpital Saint Louis, Université Paris Diderot, Paris, France
Françoise Bernaudin
Centre de référence de drépanocytose, CHIC Centre Hospitalier Intercommunal de Créteil, Créteil, France
Dominique Bories
Hématologie Moléculaire, Hôpital Henri Mondor, Université Paris Est, Créteil, France
Marina Cavazzana
Department of Biotherapy, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM CIC 1416, Paris, France;Paris Descartes–Sorbonne Paris Cité University, Imagine Institute, Paris;Human Lymphohematopoiesis Laboratory, Inserm UMR 1163, Imagine Institute, University Paris Descartes Sorbonne Paris Cité, Paris, France
Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism
