Purpose: To evaluate the safety and hematopoietic activity of daniplestim administered concurrently with granulocyte colony- stimulating factor (G-CSF) for peripheral-blood stem-cell (PBSC) mobilization. Patients and Methods: In the initial dose- escalation phase, 25 patients with adenocarcinoma of the breast (AB; 13 patients) or lymphoma (12 patients) were given daniplestim at doses ranging from 0.1 to 3.75 μg/kg/d plus G-CSF 10μg/kg/d. In the randomized phase 52 patients with AB (27 patients) or lymphoma (25 patients) were randomized within disease categories to the daniplestim dose chosen in the dose- escalation phase plus G-CSF 10 μg/kg/d (D+G) or placebo plus G- CSF 10 μg/kg/d (P+G) for up to 7 days. Results: A daniplestim dose of 2.5 μg/kg/d was chosen for further study because it was hematopoietically active and had an acceptable side-effect profile. In the randomized phase, in patients with AB, D+G was associated with a higher probability (P = .0696) of collecting ≥ 2.4 x 106 CD34+ cells/kg and significantly higher circulating CD34+ cell counts (P = .0498) on days 6 through 9 after the initiation of dosing. The target level was more likely to be reached with additional leukaphereses in the patients given D+G. Patients given P+G did not benefit from additional leukaphereses beyond the first procedure. The type of mobilization did show a trend toward a shorter duration of neutropenia in the D+G group. The adverse events with D+G consisted largely of mild to moderate flu-like symptoms, including headache and fever, and occurred more frequently than with P+G. Conclusion: Daniplestim administered at 2.5 μg/kg/d is tolerable and active when combined with G-CSF, and the combination may prove more effective than G-CSF alone in promoting the collection of adequate numbers of CD34+ cells for PBSC infusion in patients with AB. (C) 2000 by American Society of Clinical Oncology.