Amifostine protects normal pluripotent peripheral blood stem cells against the toxicity of idarubicin

Abstract

Abstract Amifostine (WR2721) is a phosphorylated aminothiol compound. Previous studies have already shown the cytoprotective efficacy of Amifostine (A) on normal pluripotent peripheral stem cells (PPBSC) against the myelosuppressive effects of cyclophosphamide, melphalan and cisplatin. The purpose of the study is to determine whether A protects the normal PPBSC from the cytotoxicity of Idarubicin (IDA). Formation of multipotent progenitors colony forming units CFU-GEMM, CFU-GM and BFU-E was evaluated using a clonogenic assay. PPBSC were collected from AML and NHL patients in CR after mobilization (G-CSF±cyclo). The cytoprotective role of A was assessed after a short drug exposure of PPBSC to IDA (0.05 μg/ml for 90 min) which had been or not pretreated with A (3 mg/ml for 15 min). Progenitor cells were plated in methylcellulose in the presence of the appropriate growth factors. The number of colonies of the pretreated cells with A and then incubated with IDA was compared to the number of colonies of untreated cells with A and incubated with IDA alone. Colony growth was scored after 14 days of incubation and the results are summarized in the table. We conclude that Amifostine pretreatment can protect normal pluripotent peripheral blood stem cells from Idarubicin toxicity.