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

• Published in: Blood 1990-10, Vol.76 (7), p.1299-1307
• Main Authors: NAGLER, A, BINET, C, MACKICHAN, M. L, NEGRIN, R, BDANGS, C, DONLON, T, GREENBERG, P
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow - pathology; Cell Differentiation - drug effects; Cell Division - drug effects; Cells, Cultured; Evaluation Studies as Topic; Female; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte Colony-Stimulating Factor - therapeutic use; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Hematologic and hematopoietic diseases; Hematopoiesis - drug effects; Humans; Karyotyping; Male; Medical sciences; Middle Aged; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - pathology; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V76.7.1299.1299

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.