Stimulation of myelopoiesis in patients with aplastic anemia by recombinant human granulocyte-macrophage colony-stimulating factor.
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.
Vadhan-Raj
S
S
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Centre, Houston 77030.
Buescher
S
S
Broxmeyer
H E
HE
LeMaistre
A
A
Lepe-Zuniga
J L
JL
Ventura
G
G
Jeha
S
S
Horwitz
L J
LJ
Trujillo
J M
JM
Gillis
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D001853:Bone Marrow / Q000187:drug effects* / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor