Stimulation of myelopoiesis in patients with aplastic anemia by recombinant human granulocyte-macrophage colony-stimulating factor.

Abstract

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 granulocyte-macrophage colony-stimulating factor (GM-CSF) in aplastic anemia, we gave GM-CSF (60 to 500 micrograms 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 greater than 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.

• Authors: S Vadhan-Raj, S Buescher, H E Broxmeyer, A LeMaistre, J L Lepe-Zuniga, G Ventura, S Jeha, L J Horwitz, J M Trujillo, S Gillis
• Journal: The New England journal of medicine (N Engl J Med) Vol. 319 Issue 25 Pg. 1628-34 (Dec 22 1988) ISSN: 0028-4793 [Print] United States
• PMID: 3059191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Colony-Stimulating Factors
• Growth Substances
• Recombinant Proteins
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adolescent
• Adult
• Aged
• Anemia, Aplastic (blood, physiopathology, therapy)
• Bone Marrow (drug effects, physiopathology)
• Chemotaxis, Leukocyte
• Colony-Stimulating Factors (therapeutic use)
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor
• Growth Substances (therapeutic use)
• Hematopoiesis (drug effects)
• Humans
• Leukocyte Count
• Male
• Middle Aged
• Recombinant Proteins (therapeutic use)