Continuous infusion of macrophage inflammatory protein MIP-1alpha enhances leucocyte recovery and haemopoietic progenitor cell mobilization after cyclophosphamide

Abstract

Macrophage inflammatory protein 1alpha (MIP-1alpha) inhibits haemopoietic stem cell proliferation. This property has been exploited in a murine chemotherapy model and has been shown to ameliorate cytotoxic-induced myelosuppression after S-phase-specific cytotoxic therapy. We have now shown that BB-10010, a stable mutant of MIP-1alpha, (a) is more effective when administered as a continuous infusion than when bolus injected and (b), when administered via a 7-day infusion during and after cyclophosphamide treatment, results in an earlier recovery of leucocyte numbers. This effect was accompanied by progenitor cell mobilization into the peripheral blood and included primitive cells with marrow-repopulating ability (MRA). Maximal mobilization and recovery of leucocytes occurred when MIP-1alpha was combined with granulocyte colony-stimulating factor (G-CSF) therapy. The findings suggest that MIP1-alpha used alone or in combination with G-CSF may allow delivery of a greater chemotherapy dose intensity as a consequence of both accelerated leucocyte recovery and maintenance of high-quality mobilized progenitor cells for harvesting and peripheral blood stem cell transplantation.