GRANULOCYTE-COLONY-STIMULATING FACTOR IN ACUTE MYELOID-LEUKEMIA

The clinical application of recombinant human G-CSF in patients with a cute myeloid leukemia (AML) has been controversial because it stimulat es the in vitro proliferation of leukemic cells. In order to explore t he possibility of predicting in vivo leukemic proliferation after G-CS F administration to AML patients by using in vitro assays, we investig ated the leukemic blasts of 30 AML patients, including 14 patients who received G-CSF for severe infection associated with neutropenia follo wing chemotherapy (G-CSF group) and 16 patients who did not (control g roup). Of the 14 patients in the G-CSF group, 9 showed an increase of leukemic blasts in the peripheral blood during G-CSF administration, w hile 11 of the 16 control patients developed leukemic resurgence. In t he G-CSF group, the frequency of leukemic resurgence among patients wh ose blasts showed dose-dependent proliferation after addition of G-CSF to cultures was similar to that among patients whose blasts did not. In addition, there mere no significant differences between the G-CSF a nd control groups in [H-3]thymidine incorporation by leukemic cells an d leukemic colony formation after the addition of G-CSF to cultures. T he G-CSF receptor affinity of leukemic blasts was significantly higher in the patients with leukemic resurgence (mean dissociation constant [Kd]: 55 pM in the G-CSF group and 63 pM in the control group) than in those without it (101 pM and 96 phl, respectively), and the number of G-CSF receptors per cell was significantly lower when leukemic resurg ence occurred (200 in the G-CSF group and 260 in the control group) th an when it did not (3400 and 3030, respectively). Immunophenotyping (f or CD2, CD7, CD10, CD13, CD19, CD33, CD34, CD71, HLA-DR, glycophorin A and the G-CSF receptor) revealed no significant differences between b lasts from the patients with and without leukemic resurgence in the G- CSF group. Thus, we conclude that the in vivo leukemic resurgence duri ng G-CSF administration after chemotherapy for AML was not correlated with the in vitro responsiveness of leukemic blasts to this cytokine o r with blast phenotyping data. Leukemic resurgence is likely to occur in patients whose leukemic blasts have fewer numbers of G-CSF receptor s with a high affinity irrespective of whether patients receive G-CSF.