Ex vivo pharmacological purging of leukapheresis collections with nitrogenmustard: Amifostine pretreatment improves both early and late peripheral blood progenitor cell recovery

Ex vivo pharmacological purging of bone marrow has been used to eliminate c lonogenic tumor cells contaminating the autograft and potentially responsib le of relapse. A considerable improvement of pharmacological purging would be achieved only if normal marrow progenitor cells could be selectively pro tected by the cytotoxicity of these agents. Amifostine (WR-2721; Ethyol), a phosphorylated aminothiol compound, has been shown to have this property b oth in vivo and in vitro. We describe here, an experimental. model for ex v ivo purging of peripheral blood progenitor cell (PBPC) collections based on the combination of 3 mg/ml of amifostine and the alkylating agent nitrogen mustard. Amifostine pretreatment resulted in a statistically significant p rotection of normal late and early progenitor cells. Under the same experim ental conditions, we observed a 4-6 log reduction of contaminating leukemic cells (i.e. K-562 and CER-T) and in contrast to the protection of normal p eripheral blood progenitor cells, preincubation of contaminating K-562 or C EM with amifostine did not significantly alter the LD95 nitrogen mustard co ncentration. Moreover, when we tested fresh human leukemia progenitor cells , amifostine pretreatment sensitized the leukemic cells to the cytotoxic ef fects of NM. (C) 1999 International Society for Experimental Hematology. Pu blished by Elsevier Science Inc.