CD34+ cells mobilized by cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) are functionally different from CD34+ cells mobilized by G-CSF

Abstract

Mobilized peripheral blood progenitor cells (PBPC) are increasingly used as an alternative to bone marrow for autografting procedures. Currently, cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) or G-CSF alone are the most commonly used PBPC mobilization schedules. In an attempt to investigate whether the use of these two mobilization regimens could result in the collection of functionally different CD34⁺ cells, we analyzed nucleated cells (NC), CD34⁺ cells, committed progenitor cells and long-term culture initiating-cells (LTC-IC) in 52 leukaphereses from 26 patients with lymphoid malignancies, mobilized either by CY+G-CSF (n = 16) or G-CSF alone (n = 10). Thirty-four aphereses from the CY+G-CSF group and 18 aphereses from the G-CSF group were investigated. According to the study design, leukaphereses were carried out until an average number of 7 × 10⁶ CD34⁺ cells/kg body weight were collected. The mean (± s.e.m.) numbers of CD34⁺ cells mobilized per apheresis by CY+G-CSF and G-CSF were not significantly different (2.76 ± 0.6 × 10⁸ vs 2.53 ± 0.4 × 10⁸, P  0.7). This resulted from a mean number of NC that was significantly lower in the CY+G-CSF products than in the G-CSF products (12.4 ± 1.7 × 10⁹ vs 32 ± 5.4 × 10⁹, P  0.0001) and a mean incidence of CD34⁺ cells that was significantly higher in the CY+G-CSF products than in the G-CSF products (2.9 ± 0.6% vs 0.9 ± 0.2%, P  0.0018). The mean (± s.e.m.) number of CFU-GM collected per apheresis was significantly higher in the CY+G-CSF group than in the G-CSF group (37 ± 7 × 10⁶ vs 14 ± 2 × 10⁶, P  0.03). Interestingly, CY+G-CSF-mobilized CD34⁺ cells had a significantly higher plating efficiency than G-CSF-mobilized CD34⁺ cells (25.5 ± 2.9% vs 10.8 ± 1.9%, P  0.0006). In addition, the mean number of LTC-IC was significantly higher in the CY+G-CSF products than in the G-CSF products (6.3 ± 1 × 10⁶ vs 3.3 ± 0.3 × 10⁶, P  0.05). In conclusion, our data provide evidence that CY+G-CSF and G-CSF induce the mobilization of CD34⁺ cells with different clonogenic potential. As mobilized PBPC containing large numbers of progenitors lead to safer transplantation, this issue may have implications for planning mobilization strategies.