Granulocyte-macrophage colony-stimulating factor and interleukin-3 in combination: a potent and consistent myelodysplastic syndrome bone marrow stimulant in vitro.
In an effort to overcome bone marrow failure in myelodysplastic syndrome (MDS), we have investigated recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in phase I-II clinical trials. Although these agents partially increased peripheral blood granulocyte counts, their effect on other hematopoietic lineages was generally sporadic. Since in vitro analysis and in vivo studies in primates indicate that GM-CSF and IL-3 synergistically enhance hematopoietic stem cell proliferation, we evaluated their combined effect on marrow progenitors obtained from ten MDS patients. When used singly, each growth factor stimulated replication of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) colony-forming cells in a dose-dependent fashion. When colony-stimulating activity was compared at concentrations that maximally amplified individual MDS patients' colony numbers, IL-3 was a more potent stimulant in some patients and GM-CSF in others. When used in combination, IL-3 plus GM-CSF was more effective than each growth factor by itself in five of six patients. Our data indicate that the MDS hematopoietic progenitor stimulatory effect of these growth factors varies from patient to patient. However, the combination of GM-CSF and IL-3 appears to be more potent than the individual molecules in the majority of patients.
Estrov
Z
Z
Department of Clinical Immunology and Biological Therapy, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Kurzrock
R
R
Talpaz
M
M
Blake
M
M
Gutterman
J U
JU
D001853:Bone Marrow / Q000187:drug effects* / Q000503:physiopathology; D002478:Cells, Cultured; D004338:Drug Combinations; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007377:Interleukin-3 / Q000627:therapeutic use*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013268:Stimulation, Chemical
D004338:Drug Combinations; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor