title: Quantitative and qualitative analysis of the human primitive progenitor cell compartment after autologous stem cell transplantation.
abstract: The aim of this study was to examine whether the severe prolonged deficiency in marrow clonogenic progenitor cells reported after autologous stem cell transplantation (ASCT) is associated with impairment of the primitive progenitor cell compartment. We performed Dexter-type marrow cultures and limiting dilution assays with CD34(+) cells from patients 1 year and/or later after autografting with peripheral blood stem cells for non-Hodgkin's lymphoma (NHL). Flow cytometric analysis was used to assess the CD38 antigen expression and apoptotic state (7-ADD(-)/annexin-V(+) cells) of the CD34(+) cell population. We found a dramatic decrease in both clonogenic progenitor cell production and frequency of long term culture-initiating cells (LTC-IC) in all the patients tested at 1 year, even in those displaying normal progenitor cell frequency. Surprisingly, the clonogenic capacity of each LTC-IC was not increased. Flow cytometric analysis of the CD34(+) cell population confirmed this quantitative defect, with a reduction in the CD38(dim/neg) cell population but no increase in apoptosis. This defect did not improve over time up to 4 years after transplantation. In addition, qualitative abnormalities were revealed, demonstrated by decreased CD34 antigen expression, together with impaired differentiating properties of LTC-IC toward erythroid lineage at 1 year. This study indicates that both quantitative and qualitative abnormalities of the primitive progenitor cell compartment are a constant feature up to 4 years after autologous stem cell transplantation.
authors: Laboratory of Hematology and Department of Medical Oncology and Blood Diseases, University Hospital, Tours, France.
authors: Guillaume
authors: G
authors: Cartron
authors: Olivier
authors: O
authors: Herault
authors: Lotfi
authors: L
authors: Benboubker
authors: Nathalie
authors: N
authors: Clement
authors: Marie-Christine
authors: MC
authors: Bernard
authors: Francoise
authors: F
authors: Roingeard
authors: Isabelle
authors: I
authors: Desbois
authors: Philippe
authors: P
authors: Colombat
authors: Christian
authors: C
authors: Binet
authors: Jorge
authors: J
authors: Domenech
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D001854:Bone Marrow Cells / Q000166:cytology; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D005260:Female; D005500:Follow-Up Studies; D006410:Hematopoiesis; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014182:Transplantation, Autologous