Bone marrow changes in patients with refractory aplastic anemia treated by recombinant GM-CSF.
The morphologic changes in the bone marrow of eight patients with refractory aplastic anemia who received 4 or more weeks of granulocyte macrophage-colony-stimulating factor (GM-CSF) are described. All eight patients demonstrated a continuous rise in the absolute number of neutrophils, eosinophils, and monocytes over the first four weeks of therapy. Bone marrow examination revealed a progressive increase in bone marrow cellularity in all patients except one. An increase in myeloid: erythroid ratio was seen with progressive maturation of granulocytic cells. Neutrophilic and eosinophilic myelocytes were the most prominent cells. The percentage of myeloblasts and promyelocytes did not increase significantly, and the proportions of postmitotic granulocytic cells did not change either. No significant morphologic changes were noted in the basophilic, erythroid, and megakaryocytic series. The most prominent topographic observation in the bone marrow during GM-CSF therapy was the frequent clustering of myeloid cells close to the bone trabeculae. The periosteal localization of myeloid precursors may reflect a higher concentration of stem cells and/or stromal cells in the bone marrow adjacent to the bone trabeculae or a higher concentration of growth factors. Careful morphologic examination of bone marrow in CSF clinical trials will provide useful information regarding the in vivo effects of these growth factors, and will aid in the development of a rational approach to combining them for therapy.
Department of Pathology, UCLA School of Medicine 90024.
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F
Naeim
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R
Champlin
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S
Nimer
D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology*; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor