title: Biological effects of recombinant human granulocyte colony-stimulating factor in patients with untreated acute myeloid leukemia.
abstract: Hematopoietic growth factors are being administered to patients with acute myeloid leukemia (AML) both to shorten the duration of chemotherapy-induced neutropenia and in an attempt to increase cytotoxicity of cell cycle-specific agents. However, limited information is available concerning the effects of growth factors in AML patients. To examine the 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 micrograms/kg/d) administered to 28 untreated AML patients. Twenty-seven patients (96%) showed increases in at least one of the following parameters after G-CSF: blood blasts, bone marrow (BM) blasts, leukemia cells in S phase or interphase 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 (median change, %5.9%; P = .009). Interphase BM cells with trisomy 8 or monosomy 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 < .0001). Trisomy 8 or monosomy 7 was shown by fluorescence in situ hybridization in post-G-CSF blood neutrophils from 4 of 6 patients but was also present in neutrophils before G-CSF. We conclude that the percentage of leukemia cells in S phase increases and that leukemia cell populations undergo expansion during short-term administration of G-CSF in almost all AML patients.
authors.affiliation: Department of Hematologic Oncology, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Baer
authors.forename: S H
authors.initials: SH
authors.lastname: Bernstein
authors.forename: V L
authors.initials: VL
authors.lastname: Brunetto
authors.forename: K
authors.initials: K
authors.lastname: Heinonen
authors.forename: K
authors.initials: K
authors.lastname: Mrózek
authors.forename: V L
authors.initials: VL
authors.lastname: Swann
authors.forename: H
authors.initials: H
authors.lastname: Minderman
authors.forename: A W
authors.initials: AW
authors.lastname: Block
authors.forename: L A
authors.initials: LA
authors.lastname: Pixley
authors.forename: N P
authors.initials: NP
authors.lastname: Christiansen
authors.forename: J W
authors.initials: JW
authors.lastname: Fay
authors.forename: M
authors.initials: M
authors.lastname: Barcos
authors.forename: Y
authors.initials: Y
authors.lastname: Rustum
authors.forename: G P
authors.initials: GP
authors.lastname: Herzig
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000208:Acute Disease; D000782:Aneuploidy; D001772:Blood Cell Count; D002453:Cell Cycle; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D009504:Neutrophils / Q000473:pathology; D011994:Recombinant Proteins; D014314:Trisomy
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor