Chemotherapy plus G-CSF mobilized peripheral blood stem cell harvests from acute myeloid leukaemia patients contain large amounts of polyclonal myeloid linnegCD11cpos dendritic precursor cells

Br J Haematol. 2004 Mar;124(5):636-44. doi: 10.1111/j.1365-2141.2004.04818.x.

Abstract

Dendritic cells (DC) are potent antigen-presenting cells that can induce effective tumour-specific T-cell responses. This study investigated leucapheresis products as source of DC precursors in 48 patients undergoing autologous peripheral blood stem cell (PBSC) transplantation for haematological malignancies. Strikingly, high-dose cytarabine and etoposide plus granulocyte colony stimulating factor (G-CSF) mobilized PBSC harvests from acute myeloid leukaemia (AML) patients containing the highest number of myeloid lin(neg)CD11c(pos) DC (mean: 7.04 x 106/kg, range: 1.46-19.67) which was 18.1-fold higher than in non-AML patients mobilized using chemotherapy (CT) regimens plus G-CSF. Clonality of purified lin(neg)CD11c(pos) DC from CT plus G-CSF mobilized AML patients (n = 8 ) was assessed using the human androgen-receptor locus methylation, disclosing a polyclonal pattern in five female patients. These cells displayed morphological and phenotypic features of myeloid DC precursors with expression of HLA-DR, HLA-ABC, CD86, CCR5 and CD54 molecules but lacking CD80, CD83, CD1a and CD40 antigens. Short-term culture with autologous leukaemic cell lysates plus tumour necrosis factor-alpha yielded maturated myeloid DC capable of triggering interleukin-2 and interferon-gamma production by autologous T-lymphocytes. These findings suggest that the use of post-remission CT and G-CSF as mobilizing regimen in AML patients generates PBSC containing high doses of polyclonal myeloid lin(neg)CD11c(pos) DC precursors, which could be used to design feasible immunotherapy protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CD11 Antigens / analysis
  • Clone Cells
  • Dendritic Cells / pathology*
  • Feasibility Studies
  • Female
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Myeloid Cells / pathology*
  • Phenotype

Substances

  • CD11 Antigens
  • Granulocyte Colony-Stimulating Factor