The relationship between the phosphorylation of 1-β-d-arabinofuranosylcytosine (ara-C) and intracellular retention of 1-β-d-arabinofuranosylcytosine triphosphate (ara-CTP) in vitro by leukemic myeloblasts and the response of patients to treatment with ara-C and anthracycline was studied. There were quantitative differences between patients in the amount of ara-CTP initially formed and that retained intracellularly at 4 hr. On the basis of these differences, the patients could be placed into 2 subgroups: those 13 patients whose leukemic cell retention was ≥36% and the remaining 15 patients whose leukemic cells retained ≤19% ara-CTP's. Of the 13 patients in the high-retention group, 11 attained complete remission. Seven of the 11 patients remain in complete remission at 55+ to 129+ weeks. Nine of 15 patients whose ara-CTP retention was ≤19% attained complete remission. Eight of these patients have relapsed between 11 and 92 weeks, with a single patient remaining in remission at 58+ weeks. The median remission duration for this group was 28 weeks, while for the high retention it has already exceeded 63 weeks.
These data indicate that, although these patients are clinically diagnosed as acute myelocytic leukemia and treated in an identical manner, their cells metabolize ara-C differently. The data demonstrate a significant correlation between ara-CTP formation and retention in vitro by acute myelocytic leukemia cells and the duration of remission of patients receiving ara-C as part of their remission induction and maintenance therapy.
Supported in part by Project Grant CA-18420, Program Project Grant CA-21071, and Core Program Grants CA-5834 and CA-13038 from the National Cancer Institute.