title: Potentiation of granulocyte colony-stimulating factor-induced mobilization of circulating progenitor cells by seven-day pretreatment with interleukin-3.
abstract: Granulocyte colony-stimulating factor (G-CSF) as a single agent is increasingly used for the mobilization of peripheral blood progenitor cells (PBPCs) for stem cell transplantation. In patients with perturbed hematopoiesis the mobilizing capacity of G-CSF alone may be inadequate. We have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment markedly potentiated the increase in PBPC numbers by subsequent administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect of IL-3 pretreatment on G-CSF-induced mobilization of PBPCs in 6 patients with Hodgkin's disease (n = 5) or non-Hodgkin's lymphoma (n = 1) who had low progenitor cell numbers because of previous chemotherapy. Patients were treated in cycle 1 with G-CSF at a dose of 5 microgram/kg/d for 5 days and, after a treatment-free interval, received cycle 2 consisting of 5 microgram/kg/d of IL-3 for 7 days followed by G-CSF again at a dose of 5 microgram/kg/d for 5 days. G-CSF alone increased the mean number of circulating colony-forming units-GM (CFU-GM) by 21-fold, the number of burst-forming units-erythroid (BFU-E) by 9-fold, and the number of CFU-mix by 24-fold over pretreatment values. Treatment with 5 microgram/kg/d of IL-3 for 7 days did not mobilize by itself but significantly potentiated G-CSF-induced mobilization of all progenitor cell types leading to a 56-, 15-, and 46-fold increase over baseline of CFU-GM, BFU-E, and CFU-mix numbers, respectively. In 2 patients in whom leukapheresis was performed after G-CSF alone the target number of 2 x 10(6)/kg CD34+ cells was not reached. However, leukapheresis after the IL-3/G-CSF combination obtained > or =2 x 10(6)/kg CD34+ cells in 3 of 6 patients, including both patients who had inadequate collection after G-CSF alone. In one patient adequate function of mobilized progenitors could be shown by the demonstration of rapid trilineage engraftment after infusion of progenitors after myeloablative chemotherapy. Seven-day pretreatment with IL-3 may be a useful mean to augment mobilization of circulating progenitors by G-CSF. The combination of IL-3 and G-CSF seems to allow the procurement of sufficient numbers of PBPCs in some patients who cannot be mobilized adequately by G-CSF alone.
authors.affiliation: Blood Transfusion Service, Institute of Immunology, University of Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Geissler
authors.forename: C
authors.initials: C
authors.lastname: Peschel
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.forename: H
authors.initials: H
authors.lastname: Strobl
authors.forename: J
authors.initials: J
authors.lastname: Goldschmitt
authors.forename: L
authors.initials: L
authors.lastname: Ohler
authors.forename: P
authors.initials: P
authors.lastname: Bettelheim
authors.forename: P
authors.initials: P
authors.lastname: Kahls
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: P
authors.initials: P
authors.lastname: Höcker
authors.forename: K
authors.initials: K
authors.lastname: Kolbe
mesh_terms: D000328:Adult; D002452:Cell Count / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor