SENSITIVITY OF PRIMARY CLONOGENIC BLASTS FROM ACUTE LYMPHOBLASTIC-LEUKEMIA PATIENTS TO AN ACTIVATED CYCLOPHOSPHAMIDE, VIZ, MAFOSFAMIDE

Primary cyclophosphamide-naive clonogenic blasts from 32 patients with newly diagnosed acute lymphoblastic leukemia (ALL) were tested for th eir in vitro sensitivity to an ''activated'' cyclophosphamide, viz., m afosfamide, using leukemic progenitor cell (LPC) colony assays. Marked interpatient variation in the responses of LPC from newly diagnosed p atients to mafosfamide prompted assessment of mafosfamide sensitivity in relation to more frequently measured parameters of newly diagnosed ALL. Only immunophenotype and sex showed a significant association wit h the intrinsic mafosfamide sensitivity of LPC. LPC from T-lineage ALL patients were more resistant to mafosfamide than LPC from B-lineage A LL patients, as reflected by 1.8-fold and 4.3-fold higher mean SF10 an d SF20 (surviving fractions of ALL LPC at 10 and 20 mu M mafosfamide, respectively) values. LPC from male patients were more resistant to ma fosfamide than LPC from female patients, as reflected by 1.9-fold and 4.8-fold higher mean SF10 and SF20 values. In comparison to T-lineage ALL patients, a significantly greater fraction of B-lineage ALL patien ts had mafosfamide-sensitive LPC with SF10 values of <0.25 (61% vs 11% , P = 0.01). Notably, all four cases exhibiting resistance to mafosfam ide, i.e., SF20 greater than or equal to 0.5, were males with T-lineag e ALL. In order to exclude the influence of sex as a confounding facto r in the observed immunophenotype-mafosfamide sensitivity association, we also compared the mafosfamide sensitivities of LPC from male patie nts only. The means of SF10, and SF20 values of LPC from male T-lineag e ALL patients were 1.5- and 3.2-fold higher than those of LPC from ma le B-lineage ALL patients (P<0.1). Thus, in the made patient subgroup, the immunophenotype-mafosfamide sensitivity association remained sign ificant.