Variable effect of recombinant human granulocyte-macrophage colony-stimulating factor on bone marrow fibrosis in patients with myelodysplasia.
Eleven patients with myelodysplastic syndrome (MDS) and bone marrow fibrosis were identified out of a group of 15 patients with MDS who received recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) as part of a phase I/II trial. Bone marrow biopsies were obtained before and after one or more courses of GM-CSF at 250 micrograms/m2 administered as a 12-h infusion each day for 14 days. The biopsies were blindly evaluated and reticulin formation and collagen deposition were graded on a scale of 0-4. Fibrosis unequivocally increased in three patients and decreased in three patients. There were equivocal increases in an additional two patients and decreases in one subject. It was unchanged in one subject and unevaluable in one patient. Although patients in whom fibrosis increased tended to have smaller increases in neutrophil and reticulocyte counts on therapy, the difference was not statistically significant. In this small group of patients, it was not possible to determine clinical features that predicted response. Although GM-CSF can lead to partial resolution of marrow fibrosis in some individuals, it can also accelerate its deposition; improvement in granulocyte or reticulocyte count does not preclude increasing marrow fibrosis. Thus, the use of GM-CSF in patients with myelodysplasia with marrow fibrosis must be undertaken with caution.
Antin
J H
JH
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Weinberg
D S
DS
Rosenthal
D S
DS
D001706:Biopsy; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005355:Fibrosis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D011994:Recombinant Proteins; D012155:Reticulin / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D012155:Reticulin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen