Summary. Some patients unexpectedly fail to mobilize sufficient numbers of haematopoietic progenitor cells (HPCs) into the peripheral blood for autologous transplantation. Considering the important role of the chemokine stromal cell-derived factor 1 (SDF-1) in HPC homing, we investigated a possible relationship between SDF1 gene polymorphism and HPC mobilization capacity in 63 patients with malignancy. Some 67% of the good mobilizers ($ 50 CD34 1 cells/ml) and only 36% of the intermediate/poor mobilizers were SDF1-3 0 A allele carriers (P 0´032). In multivariate analysis, the presence of the SDF1-3 0 A allele was the only factor predictive of good CD341 cell mobilization (P 0´025). This is the first report showing the involvement of genetic factors for HPC mobilization in humans and suggests a significant role for SDF-1 in this process.

Summary. The roles of the chemokine stromal-derived factor 1 (SDF-1) and the matrix metalloproteinase 9 (MMP-9) in haematopoietic progenitor cell (HPC) mobilization are still unclear, particularly when patients are mobilized by granulocyte colony-stimulating factor (G-CSF) plus chemotherapy. We determined bone marrow (BM) and peripheral blood (PB) plasma levels of SDF-1, together with CXC-chemokine receptor 4 (CXCR-4) expression on CD34 + cells, and interleukin 8 (IL-8) and MMP-9 in 55 patients mobilized for autologous PB transplantation compared with 10 normal BM and PB samples. Plasma samples were tested at steady state (SS-) and after mobilization by cyclophosphamide and G-CSF administration (M-). SDF-1, CXCR-4, IL-8 and MMP-9 levels were significantly lower in SS-and M-PB than in SS-BM. Differences in SDF-1 levels between SS-PB and SS-BM were also observed after mobilization. We showed for the first time a clear relationship between the levels of circulating HPC, both at steady state and after mobilization, and those of secreted MMP-9 but not of SDF-1 or IL-8. However, a negative correlation was observed between mobilizing capacity and CXCR-4 expression on CD34 + cells. These findings suggest that G-CSF-induced mobilization of HPC from BM involves MMP-9, without reversing the positive gradient of SDF-1 between BM and PB.

This study opens new perspectives for the clinical utilisation of L-asparaginase. This mode of administration of the drug is able to improve pharmacodynamic parameters and enzymic efficacy and to increase the general tolerance of the treatment.