AMIFOSTINE PLUS GRANULOCYTE-COLONY-STIMULATING FACTOR THERAPY ENHANCES RECOVERY FROM SUPRALETHAL RADIATION EXPOSURES - PRECLINICAL EXPERIENCE IN ANIMAL-MODELS

A murine model was used to explore whether the cytoprotective agent am ifostine (WR-2721) can be used to protect a critical fraction of haemo poietic stem cells against radiation, and whether granulocyte colony-s timulating factor (G-CSF) can then be used to stimulate the protected cells to proliferate and reconstitute the haematopoietic system. Group s of C3H/HeN mice treated with 200 mg/kg amifostine i.p. 30 min before Co-60 irradiation and/or 125 mu g/kg G-CSF subcutaneously from days 1 -16 post irradiation were compared. The dose reduction factor (DRF) of the combination of amifostine and G-CSF from LD(50/30) values was gre ater than the sum of the DRFs for amifostine and G-CSF individually. A cceleration of recovery of bone marrow and splenic multipotent stem ce lls (CFU-s) and granulocyte-macrophage progenitor cells (GM-CFC), as w ell as of peripheral blood red and white cells and platelets, was grea test in mice treated with amifostine plus G-CSF. These studies suggest that amifostine and recombinant haematopoietic growth factors can be used in combination to reduce myelosuppression and lethality associate d with radiation or radiomimetic drugs.