THE EFFECT OF THE GM-CSF IL-3 FUSION PROTEIN PIXY321 ON BONE-MARROW AND CIRCULATING HEMATOPOIETIC-CELLS OF PREVIOUSLY UNTREATED PATIENTS WITH CANCER/

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 mu g/m(2) for 14d. Side-effects were mild and consisted mainly of injection-site reactions and constitutional symptoms. A bip hasic modest increase of white blood count (2 . 5-fold) and platelets (1-1 . 5-fold) was seen, accompanied by an increased bone marrow cellu larity and an increase in circulating progenitors. Colony-forming cell s in the blood rose to a median of 184 granulocyte/macrophage-colony f orming cells (GM-CFC)/ml, eight Mix-CFC/ml, 250 burst forming units-er ythroid (BFU-E)/ml and 140 CFU-mega-karyocytes/ml, corresponding to a 10-, 2 . 5-, 8- and 30-fold increase respectively. When seeded for lon g-term culture on irradiated bone marrow stroma, the mobilized cells w ere not able to sustain haemopoiesis in vitro to the same degree as bo ne marrow, Taken together, these results indicate that PIXY321 has a b iological effect in humans more similar to that of IL-3 than to that o f GM-CSF.