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

N Engl J Med. 1988 Dec 22;319(25):1628-34. doi: 10.1056/NEJM198812223192503.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia, Aplastic / blood
  • Anemia, Aplastic / physiopathology
  • Anemia, Aplastic / therapy*
  • Bone Marrow / drug effects*
  • Bone Marrow / 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

Substances

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