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In summary, the use of CSFs in patients with acquired neutropenia is mainly supportive, but may improve the prognosis in high-risk situations. A clear indication for the use CSFs is idiopathic neutropenia. In congenital neutropenia (Kostmann syndrome), for example, the patients suffer from septicemias, pneumonias, and other infections from early infancy. After treatment with G-CSF, the number of neutrophils normalizes and chronic ulcerations and infections heal. Several patients have now been treated for more than 15 yr with few side effects.
2. Pegfilgrastim Pegfilgrastim is filgrastim (G-CSF) bound to polyethylene glycol, which significantly increases the in vivo half-life compared with native recombinant G-CSF. Therefore, one injection of pegylated G-CSF per cycle of chemotherapy is sufficient to stimulate neutrophil recovery. The side effect profile is comparable to G-CSF. The indication of pegfilgrastim as approved by the FDA is to reduce the risk of neutropenia following myelosuppressive chemotherapy. The recommended dose of pegfilgrastim is 6 mg given by subcutaneous injection.
TPO is the ligand for the c-MPL receptor, which is present on early hemopoietic progenitor cells, megakaryocytes, and platelets. The m-RNA for TPO is expressed in the liver, kidney, and to a lesser extent in stromal cells of spleen and bone marrow. Signaling via c-MPL involves activation of the JAK[Janus kinase]/STAT and Ras signaling pathways. The serum levels of TPO are high in thrombocytopenic patients and low in normal individuals. TPO stimulates both the proliferation and maturation of cells committed to megakaryocyte Chapter 2 / Molecular Biology and Cytokines 33 production.