AMIFOSTINE (WR-2721) PROTECTS NORMAL HEMATOPOIETIC STEM-CELLS AGAINST CYCLOPHOSPHAMIDE DERIVATIVES TOXICITY WITHOUT COMPROMISING THEIR ANTILEUKEMIC EFFECTS

被引:18
作者
DOUAY, L
HU, C
GIARRATANA, MC
GORIN, NC
机构
关键词
AMIFOSTINE; BONE MARROW TRANSPLANTATION; STEM CELLS; LEUKEMIA;
D O I
10.1016/0959-8049(95)00146-A
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We compared the effects of amifostine (WR-2721) on the cytotoxicity of mafosfamide or 4-hydroperoxycyclophosphamide (4-HC) in normal marrow progenitor cells (CFU-GM) and leukaemic progenitor cells (CFU-L) during ex vivo purging for autologous bone marrow transplantation (ABMT). Mononuclear cells (MNC) were incubated with amifostine 3 mg/ml for 15 min, washed, and subsequently tested for their sensitivity to mafosfamide or 4-HC (20-200 mu g/10(7) MNC/ml). The LD(95) was significantly higher among amifostine-treated cells for PCM-CFU-GM in 6 of 13 patients and for 5R-CFU-GM in 4 of 10 patients (P < 0.05). In contrast, amifostine exhibited no protective effects upon CFU-L. The results of this study show that amifostine protects normal late and early progenitor cells from the toxic effects of cyclophosphamide derivatives while preserving their antileukaemic effects. These results suggest that amifostine has therapeutic value as a protective agent for normal marrow progenitor cells during ex vivo purging of bone marrow for ABMT.
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页码:S14 / S16
页数:3
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