Purging of G-CSF-mobilized peripheral autografts in acute leukemia with mafosfamide and amifostine to protect normal progenitor cells

In the present study the in vitro growth of CFU-GM from PBPC of patients wi th AML (n = 11), purged with mafosfamide alone or a combination of mafosfam ide and amifostine, was compared to historical controls of mafosfamide-purg ed bone marrow (AML CR1, n = 16). Two patients were transplanted with mafos famide and mafosfamide/amifostine pretreated PBPC autografts, The in vitro experiments demonstrated a significantly higher resistance of peripheral bl ood derived CFU-GM to mafosfamide (median ID95 190 mu g mafosfamide/ml) com pared with bone marrow derived CFU-GM (median ID95 130 mu g/ml). Preincubat ion with amifostine significantly further increased the median ID95 to 245 mu g/ml. The clinical results showed short recovery times for neutrophils > 500/mu l (9 and 13 days) and platelets >20 000/mu l (12 and 21 days) and st able long-term engraftment with one relapse at day +118 and one patient in CR at day 760 after transplantation. The in vitro results show a significan t advantage of PBPC over bone marrow-derived progenitors for purging with m afosfamide. Furthermore, a protective effect from mafosfamide of amifostine on normal progenitors could be demonstrated, The clinical results demonstr ate the clinical feasibility of using mafosfamide-purged autologous PBPCT w ithout impairing the short-term and long-term repopulating capacities of th e autografts.