Amifostine (WR-2721) protects normal haematopoietic stem cells against cyclophosphamide derivatives' toxicity without compromising their antileukaemic effects.
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 micrograms/ 10(7) MNC/ml). The LD95 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 will show that amifostine protects normal late and early progenitor cells for 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.
Douay
L
L
University of Paris-Saint-Antoine Medicine School, Hôpital d'enfants, Paris, France.
Hu
C
C
Giarratana
M C
MC
Gorin
N C
NC
D004999:Amifostine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*
D000970:Antineoplastic Agents; C048341:mafosfamide; D003520:Cyclophosphamide; D004999:Amifostine; C011272:perfosfamide