IN-VIVO BIOLOGIC EFFECTS OF PIXY321, A SYNTHETIC HYBRID PROTEIN OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-3 IN CANCER-PATIENTS WITH NORMAL HEMATOPOIESIS - A PHASE-I STUDY

PIXY321 is a novel fusion protein of recombinant human granulocyte-mac rophage colony-stimulating factor and interleukin-3 that exhibits biol ogic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injecti on twice daily at doses of 25 to 1,000 mu g/m(2)/day over 14 days to 2 4 patients with sarcoma before chemotherapy as part of a phase I trial . The treatment was associated with significant increases in white blo od cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count w as gradual and peaked after the cessation of the cytokine treatment an d was not clearly dose related. PIXY321 treatment also increased bone marrow (BMI) cellularity and the percentage of BMI cells in S phase (P < .001), In addition, there was a significant increase in the number of CD34(+) cells and committed and multipotential progenitors in the p eripheral blood, The ex vivo expansion capacity of peripheral blood an d BM progenitor cells was preserved after the in vivo treatment with P IXY321, The treatment was well tolerated, with the most common side-ef fect being injection site reactions. The results of this study show th e biologic and clinical activity of a genetically engineered fusion mo lecule of two hematopoietic cytokines in humans with normal hematopoie tic function. (C) 1995 by The American Society of Hematology.