The use of granulocyte-macrophage colony-stimulating factor to enhance hematologic parameters of patients with cirrhosis and hypersplenism

In patients with end-stage liver disease complicated with hypersplenism, neutropenia and thrombocytopenia are risk factors for systemic sepsis and spontaneous bleeding. Granulocyte-macrophage colony-stimulating factor is a naturally occurring cytokine that promotes proliferation and differentiation of granulocyte and monocyte progeny cells. In addition, it is reported to promote the proliferation of megakaryocytes. Its use as an intravenous infusion is Federal Drug Authority (USA) approved for the enhancement of myeloid recovery following autologous bone-marrow transplantation. The present study was initiated to determine whether granulocyte-macrophage colony-stimulating factor could be used to increase the white blood cell and platelet count in patients with cirrhosis and hypersplenism and to determine whether the more convenient subcutaneous route can be used with the same efficacy as the recommended intravenous route. Nine patients with cirrhosis and hypersplenism manifested by a reduced absolute neutrophil count (mean value of 1300±200/mm³) were studied. In eight patients, Indium white blood cell splenic sequestration scans were obtained before and after the administration of granulocyte-macrophage colony-stimulating factor intravenous infusion or subcutaneously for 7 days. One patient had to discontinue the therapy due to a reaction to granulocyte-macrophage colony-stimulating factor. Following intravenous infusion of granulocyte-macrophage colony-stimulating factor, the mean absolute neutrophil count increased to 2600±1100/mm³. Following subcutaneous administration, the mean absolute neutrophil count increased to 4100±200/mm³. No significant change in platelet count occurred with either route of administration. Indium scans obtained before and after the treatment period revealed no significant difference in the splenic uptake. Based upon these data, it can be concluded that: 1) Granulocyte-macrophage colony-stimulating factor can be used to increase the white blood cells and the absolute neutrophil count, but not the platelet count of patients with cirrhosis and hyper-splenism; 2) The more convenient subcutaneous route is as efficient as the Federal Drug Authority (USA) approved intravenous route; and 3) No change in the fraction of white blood cells sequestered in the spleen was observed following granulocyte-macrophage colony-stimulating factor administration.