Aplastic anemia is a syndrome in which pancytopenia occurs in the presence of hypocellularity of the bone marrow. To assess the biologic activities of recombinant human granulocytemacrophage colony-stimulating factor (GM-CSF) in aplastic anemia, we gave GM-CSF (60 to 500 μg per square meter of body-surface area) to 10 patients with moderate or severe disease, by continuous intravenous infusion daily for two weeks, and repeated the treatment after a two-week rest period. The treatment increased the white-cell count (1.6- to 10-fold) in all patients, primarily because of an increase in the numbers of neutrophils (1.5- to 20-fold), eosinophils (12- to >70-fold), and monocytes (2- to 32-fold). Rates of hydrogen peroxide production in purified granulocyte fractions increased during GM-CSF treatment. Increases in bone marrow cellularity, myeloid precursor cells, and myeloid:erythroid cell ratios accompanied the white-cell response. Despite the in vivo response of the white cells, the concentration of colony-forming cells remained the same. Measurable concentrations of interleukin-2 (2 to 15 units per milliliter) were found in the serum of 8 patients, and high levels of erythropoietin (81 to 1200 IU per liter) were found in 10 patients. The predominant side effects were constitutional symptoms. These results indicate that recombinant human GM-CSF is effective in stimulating myelopoiesis in patients with severe aplastic anemia and may benefit some patients in whom the disorder is refractory to standard forms of therapy. (N Engl J Med 1988; 319:1628–34.) APLASTIC anemia is a hematopoietic disorder characterized by bone marrow failure and pancytopenia. Several mechanisms have been implicated in the pathogenesis of this disease, including the loss of pluripotent stem cells, dysfunction of progenitor cells, defects in the microenvironment of the bone marrow, abnormalities of humoral regulators of hematopoiesis, and autoimmune inhibition of hematopoiesis.1 2 3 4 5 Transplantation of bone marrow from a histocompatible donor is currently the treatment of choice for patients under the age of 40.6 7 8 This choice is not available, however, to a majority of patients with severe aplastic anemia, because they either are older or lack a histocompatible donor.
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