Growth factors and hemostasis: differential effects of GM-CSF and G-CSF on coagulation activation--laboratory and clinical evidence.
Granulocyte-macrophage (GM-CSF) and granulocyte colony-stimulating factors (G-CSF) are equally effective hematopoietic growth factors in terms of their potential to shorten the period of neutropenia following high-dose chemotherapy or to mobilize hematopoietic stem cells. Thus the choice between the two preparations must be based on a comparison of adverse effects. Both GM-CSF and G-CSF have been implicated in disturbances of the hemostatic system, resulting in both hemorrhagic and thrombotic complications. We therefore studied the effects of GM-CSF and G-CSF therapy on hemostasis both ex vivo and clinically. In a prospective, non-randomized study 34 patients who were treated with a myeloablative regimen according to the hyper-ME+/-C protocol and stem cell or bone marrow transplantation received posttransplantation hematopoietic support with GM-CSF (n=15) or G-CSF (n=19). The patients were monitored for alterations in plasmatic coagulation parameters and clinical evidence of hemorrhagic or thrombotic events. GM-CSF, but not G-CSF, induced a significant, albeit usually mild activation of the coagulation cascade. We observed an increased frequency of veno-occlusive disease in the GM-CSF group (3/15 vs. 1/19 on G-CSF, n.s.). Other thrombotic events were rare. At the same time, hemorrhage was both more common and more severe in GM-CSF treated patients than in those on G-CSF (macroscopic hemorrhage 11/15 vs. 10/19, III hemorrhage 7/15 vs. 1/19 on GM-CSF or G-CSF, respectively). In conclusion, unlike G-CSF, if given after hyper-ME chemotherapy plus stem cell or bone marrow transplantation, at the dosage used here GM-CSF induced an activation of the coagulation system and was associated with an increased risk of hemostasis associated treatment complications.
Bönig
H
H
Department of Pediatric Hematology and Oncology, Center of Child Health, Heinrich Heine University Medical Center, Düsseldorf, Germany.
Burdach
S
S
Göbel
U
U
Nürnberger
W
W
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D006487:Hemostasis / Q000187:drug effects*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage; D011446:Prospective Studies
D019653:Myeloablative Agonists; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor