Recombinant human granulocyte-macrophage colony-stimulating factor plus erythropoietin for the treatment of cytopenias in patients with myelodysplastic syndromes.
In vitro studies have indicated that granulocyte-macrophage colony-stimulating factor (GM-CSF) synergizes with erythropoietin (EPO) for the production of erythroid precursors in patients with myelodysplastic syndrome (MDS). We performed a clinical trial to evaluate whether the combination of these growth factors was effective in relieving the cytopenias associated with MDS. 31 anaemic patients with low and intermediate-risk primary MDS were enrolled in a 12-week study. Therapy was initiated with GM-CSF at 1 microgram/kg/d.s.c., and then adjusted to either normalize or double the absolute neutrophil count. EPO was given subcutaneously on alternate days starting from day 2. The EPO dose was initiated at 150 U/kg and increased to 300 U/kg if after 6 weeks there was no or suboptimal erythroid response. 26 patients completed the study treatment. All evaluable cases had a neutrophil response. Clinically significant erythroid responses with increases of haemoglobin levels of at least 1 g/dl and/or reduction of transfusion needs were seen in 9/26 (34.6%), five patients improving their response after dose escalation of EPO. Treatment had no apparent effect on mean platelet counts, a single case displaying a trilineage response. An elevated bone marrow erythroid infiltration and low concentrations of circulating tumour necrosis factor-alpha were the only predictors of haemoglobin response both in univariate and in multivariate analysis. We conclude that the combination GM-CSF + EPO can abrogate neutropenia and substantially relieve transfusion requirements in a large proportion of patients with low and intermediate risk MDS. However, in vivo synergy between these growth factors for the production of erythroid precursors is not supported by our data.
Stasi
R
R
Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale, Italy. roberto.stasi@schering-plough.it
Pagano
A
A
Terzoli
E
E
Amadori
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006402:Hematologic Diseases / Q000209:etiology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications*; D010976:Platelet Count
D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor