1118 Amifostine improves the antileukemic therapeutic index of mafosfamide: Implications for bone marrow purging

Abstract

To test the potential use of amifostine (Ami) to protect normal bone marrow (N1 BM) progenitor cells during ex vivo purging of leukemia, the dose response of mafosfamide (Mfs) ± Ami on N1 BM progenitor cells was determined and the LD95 was calculated. Ami pretreatment resulted in a statistically significant protection of CFU-GM and erythroid blast-forming units (BFU-E) from Mfs toxicity. The mean ± SEM μg/ml LD95 concentrations were: CFU-GM, Mfs alone 54 ± 13 vs Ami-Mfs 66 ± 14, p. 005, BFU-E, Mfs alone 48 ± 14, vs Ami-Mfs 61 ± 11, p .005. In contrast, Ami pretreatment sensitized CFU-L to Mfs toxicity: LD95 for Mfs alone 33 ± 4 vs Ami-Mfs 27 ± 3, p .003. At the LD95 fur CFU-GM and BFU-E, Mfs alone resulted in a ≈4 log cell-kill for L-CFU. Ami protection of N1 BM resulting in a higher Mfs LD95 concentration, coupled with the Ami-sensitization of the leukemia, provided an estimated additional 6+ log leukemia cell-kill. This enhanced selective leukemia cell-kill from Mfs during ex vivo purging using the LD95 concentration of Mfs for normal marrow progenitors offers the potential for lowering the incidence of leukemic relapse while preserving a greater number of normal progenitor cells for engraftment following autologous transplantation.