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A Nagler, C Binet, ML Mackichan, R Negrin, C Bangs, T Donlon and P Greenberg
Department of Medicine, Stanford University Medical Center, CA 94305.
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.
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