Effect of in vivo treatment with rh GM-CSF on in vitro growth of haematopoietic progenitors in patients with myelodysplastic syndromes.
BACKGROUND
Recombinant (r) human (h) granulocyte/macrophage colony stimulating factor (rh GM-CSF) has been shown to increase the number of peripheral blood (PB) neutrophils, eosinophils and monocytes in myelodysplastic syndromes (MDS). The aims of this study were: 1) to evaluate the effect of rh GM-CSF therapy on the in vitro growth of granulocyte-erythroid-macrophage-megakaryocyte colonies (CFU-GEMM), erythroid colonies (BFU-E), and granulocyte-macrophage colonies (CFU-GM) in patients with MDS; 2) to assess in these patients, while they are being treated in vivo with rh GM-CSF, the possible additive effect of rh IL-3 and rh G-CSF on the in vitro growth of haematopoietic progenitors.


METHODS
The in vitro growth of CFU-GEMM, BFU-E and CFU-GM was studies in 10 myelodysplastic (MDS) patients, before and after in vivo administration of rh GM-CSF.


RESULTS
After rh GM-CSF administration, the number of CFU-GM increased in all standard risk MDS patients. In 2 out of 5 cases, this effect was more pronounced and persisted up to 30 days after the end of rh GM-CSF treatment. On the other hand, the number of CFU-GEMM and BFU-E was substantially unchanged. When rh GM-CSF, rh G-CSF and rh IL-3 were added in vitro alone or in combination as the source of colony stimulating activity, no significant increase of the CFU-GM colony number was noticed.


CONCLUSIONS
Rh GM-CSF therapy appears useful for increasing the number of peripheral blood granulocytes and of marrow CFU-GM in standard-risk MDS patients. High-risk MDS patients are far less responsive to rh GM-CSF treatment, probably reflecting a more aggressive and/or advanced disease.
Visani
G
G
Istituto di Ematologia L. e A. Seràgnoli, Università di Bologna, Italy.
Tosi
P
P
Finelli
C
C
Gamberi
B
B
Zauli
G
G
Cenacchi
A
A
Fogli
M
M
Colombini
R
R
Tura
S
S
D003114:Colony-Forming Units Assay; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007377:Interleukin-3 / Q000494:pharmacology; D008297:Male; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
D007155:Immunologic Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor