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.

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.