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Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy

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 c...

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Autores principales: Magnani, Alessandra, Pondarré, Corinne, Bouazza, Naïm, Magalon, Jeremy, Miccio, Annarita, Six, Emmanuelle, Roudaut, Cecile, Arnaud, Cécile, Kamdem, Annie, Touzot, Fabien, Gabrion, Aurélie, Magrin, Elisa, Couzin, Chloé, Fusaro, Mathieu, André, Isabelle, Vernant, Jean-Paul, Gluckman, Eliane, Bernaudin, Françoise, Bories, Dominique, Cavazzana, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193509/
https://www.ncbi.nlm.nih.gov/pubmed/31537695
http://dx.doi.org/10.3324/haematol.2019.227561
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author Magnani, Alessandra
Pondarré, Corinne
Bouazza, Naïm
Magalon, Jeremy
Miccio, Annarita
Six, Emmanuelle
Roudaut, Cecile
Arnaud, Cécile
Kamdem, Annie
Touzot, Fabien
Gabrion, Aurélie
Magrin, Elisa
Couzin, Chloé
Fusaro, Mathieu
André, Isabelle
Vernant, Jean-Paul
Gluckman, Eliane
Bernaudin, Françoise
Bories, Dominique
Cavazzana, Marina
author_facet Magnani, Alessandra
Pondarré, Corinne
Bouazza, Naïm
Magalon, Jeremy
Miccio, Annarita
Six, Emmanuelle
Roudaut, Cecile
Arnaud, Cécile
Kamdem, Annie
Touzot, Fabien
Gabrion, Aurélie
Magrin, Elisa
Couzin, Chloé
Fusaro, Mathieu
André, Isabelle
Vernant, Jean-Paul
Gluckman, Eliane
Bernaudin, Françoise
Bories, Dominique
Cavazzana, Marina
author_sort Magnani, Alessandra
collection PubMed
description 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 <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e. ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach.
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spelling pubmed-71935092020-05-11 Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy Magnani, Alessandra Pondarré, Corinne Bouazza, Naïm Magalon, Jeremy Miccio, Annarita Six, Emmanuelle Roudaut, Cecile Arnaud, Cécile Kamdem, Annie Touzot, Fabien Gabrion, Aurélie Magrin, Elisa Couzin, Chloé Fusaro, Mathieu André, Isabelle Vernant, Jean-Paul Gluckman, Eliane Bernaudin, Françoise Bories, Dominique Cavazzana, Marina Haematologica Articles 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 <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e. ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach. Ferrata Storti Foundation 2020-05 /pmc/articles/PMC7193509/ /pubmed/31537695 http://dx.doi.org/10.3324/haematol.2019.227561 Text en Copyright© 2020 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Articles
Magnani, Alessandra
Pondarré, Corinne
Bouazza, Naïm
Magalon, Jeremy
Miccio, Annarita
Six, Emmanuelle
Roudaut, Cecile
Arnaud, Cécile
Kamdem, Annie
Touzot, Fabien
Gabrion, Aurélie
Magrin, Elisa
Couzin, Chloé
Fusaro, Mathieu
André, Isabelle
Vernant, Jean-Paul
Gluckman, Eliane
Bernaudin, Françoise
Bories, Dominique
Cavazzana, Marina
Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
title Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
title_full Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
title_fullStr Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
title_full_unstemmed Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
title_short Extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
title_sort extensive multilineage analysis in patients with mixed chimerism after allogeneic transplantation for sickle cell disease: insight into hematopoiesis and engraftment thresholds for gene therapy
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193509/
https://www.ncbi.nlm.nih.gov/pubmed/31537695
http://dx.doi.org/10.3324/haematol.2019.227561
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