title: The effect of the GM-CSF/IL-3 fusion protein PIXY321 on bone marrow and circulating haemopoietic cells of previously untreated patients with cancer.
abstract: This is a phase I/II study of the GM-CSF/IL-3 fusion protein (PIXY321. Patients were treated with PIXY321 at a daily subcutaneous dose of 500, 750 and 1000 micrograms/m2 for 14 d. Side-effects were mild and consisted mainly of injection-site reactions and constitutional symptoms. A biphasic modest increase of white blood count (2-5-fold) and platelets (1-1.5 fold) was seen, accompanied by an increased bone marrow cellularity and an increase in circulating progenitors. Colony-forming cells in the blood rose to a median of 184 granulocyte/macrophage-colony forming cells (GM-CFC)/ml, eight Mix-CFC/ml, 250 burst forming units-erythroid (BFU-E)/ml and 140 CFU-mega-karyocytes/ml, corresponding to a 10-, 2.5, 8- and 30-fold increase respectively. When seeded for long-term culture on irradiated bone marrow stroma, the mobilized cells were not able to sustain haemopoiesis in vitro to the same degree as bone marrow. Taken together these results indicate that PIXY321 has a biological effect in humans more similar to that of IL-3 than to that of GM-CSF.
authors.affiliation: CRC Department of Medical Oncology, Christie Hospital, Manchester.
authors.forename: M
authors.initials: M
authors.lastname: Gheilmini
authors.forename: R
authors.initials: R
authors.lastname: Pettengell
authors.forename: L H
authors.initials: LH
authors.lastname: Coutinho
authors.forename: N
authors.initials: N
authors.lastname: Testa
authors.forename: D
authors.initials: D
authors.lastname: Crowther
mesh_terms: D000328:Adult; D002452:Cell Count / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006689:Hodgkin Disease / Q000097:blood / Q000628:therapy; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D008223:Lymphoma / Q000097:blood / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000628:therapy*; D010976:Platelet Count / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
chemical_list: D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor