BIOLOGICAL EFFECTS OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR IN PATIENTS WITH UNTREATED ACUTE MYELOID-LEUKEMIA

Hematopoietic growth factors are being administered to patients with a cute myeloid leukemia (AML) both to shorten the duration of chemothera py-induced neutropenia and in an attempt to increase cytotoxicity of c ell cycle-specific agents. However, limited information is available c oncerning the effects of growth factors in AML patients. To examine th e in vivo effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on AML cells, laboratory studies were performed before and after a 72-hour intravenous infusion of G-CSF (10 mu g/kg/d) admin istered to 28 untreated AML patients. Twenty-seven patients (96%) show ed increases in at least one of the following parameters after G-CSF: blood blasts, bone marrow (BM) blasts, leukemia cells in S phase or in terphase cells with leukemia-specific markers shown by fluorescence in situ hybridization. The median paired change in absolute blast count was +2.7 x 10(9)/L (P =.0001) after G-CSF, as compared with 0.0 during the 72 hours before initiation of G-CSF. The median percentage of BM leukemia cells in S phase increased from 6.0% to 10.7% after G-CSF (me dian change, +5.9%; P =.009). Interphase BM cells with trisomy 8 or mo nosomy 7 increased in 6 of 6 patients with these abnormalities (P =.02 ), with a median percent increase of 47%. Blood neutrophil counts also increased during G-CSF (median paired change, +2.8 x 10(9)/L; P <.000 1). Trisomy 8 or monosomy 7 was shown by fluorescence in situ hybridiz ation in post-G-CSF blood neutrophils from 4 of 6 patients but was als o present in neutrophils before G-CSF. We conclude that the percentage of leukemia cells in S phase increases and that leukemic cell populat ions undergo expansion during short-term administration of G-CSF in al most all AML patients. (C) 1996 by The American Society of Hematology.