Characteristics of cells with engraftment capacity within CD34+ cell population upon G-CSF and Plerixafor mobilization

• Published in: Leukemia 2020-12, Vol.34 (12), p.3370-3381
• Main Authors: Mombled, Margaux, Rodriguez, Laura, Avalon, Maryse, Duchez, Pascale, Vlaski-Lafarge, Marija, Debeissat, Christelle, Pérard, Baptiste, Sawai, Katherine M., Pasquet, Jean Max, Bijou, Fontanet, Thévenot, Florian, Cabantous, Txomin, Ivanovic, Zoran, Brunet de la Grange, Philippe
• Format: Article
• Language: English
• Subjects: 13/100; 13/31; 38/77; 631/532/1542; 631/80; 64/60; Animals; Antigens, CD34 - metabolism; Apheresis; Cancer Research; CD34 antigen; Child; Critical Care Medicine; Female; Gene expression; Genetic aspects; Grafting; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - metabolism; Granulocyte-macrophage colony stimulating factor; Health aspects; Hematology; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Heterocyclic Compounds - therapeutic use; Humans; Intensive; Internal Medicine; Lymphoma; Lymphoma - drug therapy; Lymphoma - metabolism; Male; Medicine; Medicine & Public Health; Membrane proteins; Mice; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - metabolism; Myeloma; Oncology; Progenitor cells; Stem cell transplantation; Stem cells; Stem Cells - drug effects; Stem Cells - metabolism; Transplantation
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-020-0982-y

In the context of hematopoietic cell transplantation, hematopoietic stem cells and progenitor cells (HSC and HPC) are usually collected by apheresis following their mobilization by G-CSF alone or in combination with Plerixafor® when patients fail to respond to G-CSF alone. In medical practice, the quality of the hematopoietic graft is based on CD34 + cell content that is used to define “Good Mobilizer (GM)” or “Poor Mobilizer (PM)” patients but does not report the real HSC content of grafts. In this study, we assessed the HSC content within the CD34 + fraction of graft samples from 3 groups of patients: 1-GM patients receiving G-CSF only (GM G-CSF ), 2-PM patients receiving G-CSF only (PM G-CSF ), 3-PM patients receiving G-CSF + Plerixafor (PM G-CSF+P ). Although HSC from the 3 groups of patients displayed very similar phenotypic profiles, expression of “stemness” genes and metabolic characteristics, their capacity to engraft NSG mice differed revealing differences in terms of HSC between groups. Indeed according to mobilization regimen, we observed differences in migration capacity of HSC, as well as differences in engraftment intensity depending on the initial pathology (myeloma versus lymphoma) of patients. This suggests that mobilization regimen could strongly influence the long term engraftment efficiency of hematopoietic grafts.