CONTINUOUS-INFUSION OF MACROPHAGE INFLAMMATORY PROTEIN MIP-1-ALPHA ENHANCES LEUKOCYTE RECOVERY AND HEMATOPOIETIC PROGENITOR-CELL MOBILIZATION AFTER CYCLOPHOSPHAMIDE

Macrophage inflammatory protein 1 alpha (MIP-1 alpha) inhibits haemopo ietic stem cell proliferation. This property has been exploited in a m urine chemotherapy model and has been shown to ameliorate cytotoxic-in duced myelosuppression after S-phase-specific cytotoxic therapy. We ha ve now shown that BB-10010, a stable mutant of MIP-1 alpha, (a) is mor e effective when administered as a continuous infusion than when bolus injected and (b), when administered via a 7-day infusion during and a fter cyclophosphamide treatment, results in an earlier recovery of leu cocyte numbers. This effect was accompanied by progenitor cell mobiliz ation into the peripheral blood and included primitive cells with marr ow-repopulating ability (MRA). Maximal mobilization and recovery of le ucocytes occurred when MIP-1 alpha was combined with granulocyte colon y-stimulating factor (G-CSF) therapy. The findings suggest that MIP1-a lpha used alone or in combination with G-CSF may allow delivery of a g reater chemotherapy dose intensity as a consequence of both accelerate d leucocyte recovery and maintenance of high-quality mobilized progeni tor cells for harvesting and peripheral blood stem cell transplantatio n.