Early hemopoietic progenitors in the peripheral blood of patients with severe aplastic anemia (SAA) after treatment with antilymphocyte globulin (ALG), cyclosporin-A and G-CSF

Andrea Bacigalupo, Giovanna Piaggio, Marina Podestà, Jie Tong, Anna Pitto, Osvaldo Figari, Federica Benvenuto, Franca Vassallo, Elisabetta Tedone, Lidia Grassia, Maria Teresa Van Lint, Francesca Gualandi, Ronald Hoffman

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objective. We previously reported that patients with acquired severe aplastic anemia (SAA) treated with antilymphocyte globulin (ALG), 6-methylprednisolone, cyclosporin A (CyA) and granulocyte colony- stimulating factor (G-CSF) can mobilize peripheral blood hemopoietic progenitors (PBHP). The aim of the present study was to assess phenotypic and functional properties of these PBHP. Methods. We studied seven patients who underwent 43 leukophereses (median 5) between day +30 and +80 following ALG, while in treatment with CyA and G-CSF. Mobilized peripheral blood hemopoietic progenitors were analyzed using surface markers conventional assays for clonogenic cells (CFU-GM, BFU-E, CFU-GEMM) as well as the recently developed assay for long-term culture initiating cells (LTC-ICs). Results. The proportion of CD34+ cells ranged between 0% and 5.4% median 0.3%) CD34+DR- between 0% and 3.5% (median 0.1%) and CD8+ cells between 3.3% and 56% (median 31%). When light density mononuclear cells (MNC) were plated in vitro, we could grow colony-forming units-granulo-macrophage (CFU-GM) (range 0-45/105 MNC; norma controls 21-200/105 MNC), burst-forming units-erythroid (BFU-E)(range 0-5/105 MNC; normal controls 0-6/105 MNC), multipotent colonies (CFU-GEMM)(range 0-3/105 MNC; normal controls 0-6/105 MNC) and high proliferative potential colony-forming cells (HPP-CFC) (range 03.4/105 MNC). We studied long-term culture-initiating cells (LTC-ICs) in 18 leukophereses from 4 patients; in 7/18 samples LTC-ICs were grown at low frequency (range 0.4-2/106 MNC) (normal controls 5-130/106 MNC), and in one patient in the absence of CFU-GM growth. The total yield of LTC-ICs in two patients was 7.64 and 10.5x102/kg of body weight. Interpretation and Conclusions. This study suggests that cells with the phenotype and in vitro function of early hemopoietic progenitors are found, though in small numbers, in the peripheral blood of patients with SAA after treatment with immunosuppressants and prolonged G-CSF administration. Whether G-CSF- mobilized progenitors contribute to hemopoietic recovery in these patients remains to be determined.

Original languageEnglish
Pages (from-to)133-137
Number of pages5
JournalHaematologica
Volume82
Issue number2
Publication statusPublished - Mar 1997

Keywords

  • Hematopoiesis
  • Immunosuppressive therapy
  • Severe aplastic anemia
  • Stem cells

ASJC Scopus subject areas

  • Hematology

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