Biological potency is expressed in International Units (IU) as tested against the World Health Organization (WHO) First International Reference Standard. The specific activity of GM-CSF is approximately 2.8 x 106 IU/mL. See GM-CSF (Leukine® (sargramostim)) package insert and labeling (Appendix H) for additional details. GM-CSF is a potent cytokine that stimulates granulocytes (neutrophils, eosinophils and basophils) and monocytes, but not lymphocytes, erythrocytes, or platelets. Recombinant human GM-CSF is a 14.6 kDa globular protein consisting of 128 amino acids containing 2 intramolecular disulfide bonds and 2 potential N-linked glycosylation sites. Known adverse effects of GM-CSF include bone pain, allergic reactions, lethargy, malaise, anorexia, skin rashes, flushing, fever, and chills. At doses higher than planned in this study, weight gain may be seen along with CONFIDENTIAL Page 28 of 102 Protocol: HERCEPTIN® + E75/GM-CSF Version 3.1 ML25749 05 March 2017 breathing difficulties, blood clots, and collections of fluid around the heart or lungs, dyspnea, thromboembolic phenomena, and pleural and pericardial effusion. In the United States, GM-CSF is commercially available as Leukine® (sargramostim,expressed in yeast).