Effect of mafosfamide (ASTA-Z-7654) on the clonogenic cells in precursor-B acute lymphoblastic leukaemia: significance for ex vivo purging of bone marrow for autologous transplantation.

Lymphoblasts from 11 patients with acute lymphoblastic leukaemia (ALL) of precursor-B type were exposed to the cyclophosphamide derivative mafosfamide (ASTA-Z-7654), and examined for growth inhibition using an in vitro colony assay. Leukaemic clonogenic cells were significantly more resistant to this cytotoxic drug (mean IC50 29.2 micrograms/ml, IC90 64.8 micrograms/ml) compared with myeloid progenitors from seven normal bone marrow samples (mean IC50 9.0, IC90 19.9) (p less than 0.0001). This effect was most pronounced in the four previously treated cases examined (mean IC90 84.4 micrograms/ml). The implications of these findings for bone marrow purging with ASTA-Z in patients with ALL for autologous marrow transplantation are discussed.