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 with AML (n = 11), purged with mafosfamide alone or a combination of mafosfamide and amifostine, was compared to historical controls of mafosfamide-purged bone marrow (AML CR1, n = 16). Two patients were transplanted with mafosfamide and mafosfamide/amifostine pretreated PBPC autografts. The in vitro experiments demonstrated a significantly higher resistance of peripheral blood derived CFU-GM to mafosfamide (median ID95 190 microg mafosfamide/ml) compared with bone marrow derived CFU-GM (median ID95130 microg/ml). Preincubation with amifostine significantly further increased the median ID95 to 245 microg/ml. The clinical results showed short recovery times for neutrophils >500/microl (9 and 13 days) and platelets >20 000/microl (12 and 21 days) and stable 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 significant advantage of PBPC over bone marrow-derived progenitors for purging with mafosfamide. Furthermore, a protective effect from mafosfamide of amifostine on normal progenitors could be demonstrated. The clinical results demonstrate the clinical feasibility of using mafosfamide-purged autologous PBPCT without impairing the short-term and long-term repopulating capacities of the autografts.
Fauth
F
F
Klinikum der Johann Wolfgang Goethe Universität, Dept of Hematology and Oncology, Frankfurt, Germany.
Martin
H
H
Sonnhoff
S
S
Bialleck
H
H
Wiesneth
M
M
Mihanovic
B
B
Hoelzer
D
D
D000208:Acute Disease; D000276:Adjuvants, Immunologic; D000328:Adult; D004999:Amifostine; D001853:Bone Marrow / Q000187:drug effects; D016465:Bone Marrow Purging / Q000379:methods; D003520:Cyclophosphamide / Q000031:analogs & derivatives*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007937:Leukapheresis; D007938:Leukemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014182:Transplantation, Autologous
D000276:Adjuvants, Immunologic; D016179:Granulocyte Colony-Stimulating Factor; C048341:mafosfamide; D003520:Cyclophosphamide; D004999:Amifostine