Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes

Transfusion. 2017 Sep;57(9):2206-2215. doi: 10.1111/trf.14182. Epub 2017 Jun 5.

Abstract

Background: Peripheral blood stem cells mobilized with granulocyte-colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens.

Study design and methods: We used a recently established single-platform multicolor flow-cytometric analysis including CD45RA and CD133 to define CD34+ subpopulations and lymphocyte subsets in products obtained either after G-CSF with or without chemotherapy alone (G, n = 40) or with addition of plerixafor (GP, n = 40).

Results: Absolute numbers of white blood cells and lymphocyte subtypes were significantly higher after plerixafor, which was not observed for absolute CD34+ counts. However, distinct differences in terms of CD34+ subtypes were observed. The most primitive multipotent progenitors (CD45RA-CD133+CD34+CD38low ) predominated significantly after G (median, 49.2%; range, 15.2%-63%) compared to GP (median, 34.4%; range, 12%-62%; p < 0.001), whereas more differentiated subsets clearly prevailed after GP.

Conclusion: In contrast to the findings of other authors, our study shows a clear shift toward more committed CD34+ subsets after plerixafor in poor mobilizers and elucidates the importance of informative surface markers like CD45RA and CD133 in addition to CD38 to discriminate earlier from more committed CD34+ cells. Further studies are needed to analyze whether these findings have an impact on clinical outcome.

MeSH terms

  • AC133 Antigen / analysis
  • ADP-ribosyl Cyclase 1 / analysis
  • Adolescent
  • Adult
  • Aged
  • Antigens, CD34 / analysis*
  • Benzylamines
  • Cell Differentiation / drug effects
  • Cyclams
  • Drug Therapy, Combination
  • Female
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cell Mobilization / standards
  • Heterocyclic Compounds / pharmacology*
  • Heterocyclic Compounds / therapeutic use
  • Humans
  • Leukocyte Common Antigens
  • Lymphocyte Subsets / cytology*
  • Male
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • T-Lymphocyte Subsets / cytology
  • Young Adult

Substances

  • AC133 Antigen
  • Antigens, CD34
  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Membrane Glycoproteins
  • PROM1 protein, human
  • Granulocyte Colony-Stimulating Factor
  • Leukocyte Common Antigens
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • plerixafor