Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-monocyte CSF.
Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA], 14 refractory anemia with excess of blasts [RAEB], 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB], respectively, P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB, respectively, P less than .05), whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB, respectively). In contrast, granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients), while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including, for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9, respectively (P less than .025). For MDS patients with normal cytogenetics, G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%), respectively (P less than .025), contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics, respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for RAEB/RAEB-T patients and those with normal cytogenetics.
Department of Medicine, Stanford University Medical Center, CA 94305.
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Nagler
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Binet
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Mackichan
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Negrin
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Bangs
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Donlon
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Greenberg
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005069:Evaluation Studies as Topic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor