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

Leukemia. 2020 Dec;34(12):3370-3381. doi: 10.1038/s41375-020-0982-y. Epub 2020 Jul 20.

Abstract

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 (GMG-CSF), 2-PM patients receiving G-CSF only (PMG-CSF), 3-PM patients receiving G-CSF + Plerixafor (PMG-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism*
  • Benzylamines
  • Child
  • Cyclams
  • Female
  • Granulocyte Colony-Stimulating Factor / metabolism*
  • Hematopoietic Stem Cell Mobilization / methods
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Heterocyclic Compounds / therapeutic use*
  • Humans
  • Lymphoma / drug therapy
  • Lymphoma / metabolism
  • Male
  • Mice
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / metabolism
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Antigens, CD34
  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Granulocyte Colony-Stimulating Factor
  • plerixafor