Controlled clinical trials indicate that amifostine (WR-2721, Ethyol) confers 
protection from the cumulative hematologic toxicities associated with alkylating 
agents and organoplatinums. To determine whether amifostine protects primitive 
hematopoietic progenitors from the cytotoxicity of functionally diverse 
antineoplastics, formation of the multipotent hematopoietic progenitors 
colony-forming units-granulocyte-erythroid, macrophage, megakaryocyte (CFU-GEMM) 
and erythroid burst-forming units (BFU-E) was evaluated using a clonogenic 
progenitor inhibition assay. Bone marrow mononuclear cells from normal donors 
were subjected to a 15-minute exposure of medium, amifostine (500 micromol/L), 
or WR-1065 (100 micromol/L at concentrations approximating peak plasma levels, 
washed twice, then treated with the antineoplastic for 1 to 6 hours. Colony 
growth was scored after 14 days of incubation. Amifostine conferred protection 
against a broader range of antineoplastics than did WR-1065. Amifostine 
protected CFU-GEMM against cytotoxicity from daunorubicin, mitoxantrone, and 
paclitaxel (range, 1.29- to 9.57-fold) (P < .05) but did not afford protection 
against cisplatin, diaziquone, or thiotepa. Similarly, amifostine protected 
BFU-E against toxicity from doxorubicin, mitoxantrone, paclitaxel, cisplatin, 
and diaziquone, yielding 3.4- to 65-fold greater colony recovery compared with 
controls. The high degree of cytoprotection afforded by amifostine derived 
largely from stimulation of progenitor growth at sublethal chemotherapy 
concentrations. In the absence of antineoplastic exposure, preincubation with 
amifostine or WR-1065 enhanced the colony-forming capacity of bone marrow 
progenitors from six normal donors, increasing recovery of CFU-GEMM and BFU-E up 
to sevenfold. We conclude that amifostine protects primitive hematopoietic 
progenitors from a wide range of antineoplastics. This broad hemoprotective 
effect derives in part from inherent trophic effects on progenitor growth and 
survival.