scholarly journals Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2482-2489 ◽  
Author(s):  
T Hartung ◽  
WD Docke ◽  
F Gantner ◽  
G Krieger ◽  
A Sauer ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Interleukin 1 ◽  
Randomized Study ◽  
Muramyl Dipeptide ◽  
Cytokine Response ◽  
Complement Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Double Blind ◽  
Stimulating Factor

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.

Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.

1997 ◽  
Vol 15 (3) ◽  
pp. 1163-1170 ◽  
Author(s):  
P L Mitchell ◽  
B Morland ◽  
M C Stevens ◽  
G Dick ◽  
D Easlea ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Hospital Stay ◽  
Pediatric Patients ◽  
Randomized Study ◽  
Severe Neutropenia ◽  
Double Blind Study ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Double Blind ◽  
Stimulating Factor

PURPOSE Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.

Priming with Granulocyte-Colony Stimulating Factor Did Not Improve Outcome in a Randomized Study of Elderly Acute Myeloid Leukemia but Increased Induction Mortality.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1980-1980 ◽  
Author(s):  
Gesine Bug ◽  
Steffen Koschmieder ◽  
Juergen Krauter ◽  
Stefanie Wiebe ◽  
Carla Hannig ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Randomized Study ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Secondary Aml ◽  
To Receive ◽  
Stimulating Factor ◽  
Acute Myeloid

Abstract Introduction: In acute myeloid leukemia (AML), granulocyte-colony stimulating factor (G-CSF) has been used in combination with induction chemotherapy to improve complete remission rates (CR) by sensitization of leukemic cells. This randomized prospective oligocenter study was designed to assess whether two induction cycles given simultaneously with and followed by G-CSF (G-CSFpriming) was superior to G-CSF administered only after induction (G-CSFpost) with regard to CR and disease-free survival (DFS) in patients older than 60 years. Secondary objectives were comparison of this concept in de novo versus secondary AML and to examine the feasibility of autologous stem cell transplantation (ASCT) as late consolidation. Methods: Overall, 183 eligible pts (median age 67 yrs) were randomly assigned to receive G-CSF starting on the day before (n=91) or after chemotherapy (n=92) during two induction cycles consisting of idarubicin, cytarabine and etoposide (IdAV). The two treatment groups were evenly matched with respect to age, diagnosis and cytogenetic risk factors. G-CSF was given as daily s.c. injection at 5μg/kg. Pts achieving a CR were scheduled to receive early consolidation chemotherapy with fludarabine, cytarabine, idarubicin plus G-CSF (mini-FlagIda) and peripheral blood stem cell (PBSC) harvest, followed by ASCT as late consolidation. Pts lacking PBSC due to mobilization failure were optionally treated with a second cycle of mini-FlagIda as late consolidation. Results: After induction chemotherapy, 118 out of 183 pts (64%) achieved CR. Response was not different in the G-CSFpost vs. G-CSFpriming group (70% vs. 59%, p=0.148). Recovery of neutrophils was similar in both groups after cycle 1 (21.8 vs. 20.5 days) and cycle 2 (14.9 vs. 16.3 days). Notably, G-CSF priming resulted in a significantly increased mortality in induction 1 (25% vs. 9%, p=0.003) associated with a higher rate of severe mucositis and infectious complications. The probability of OS and DFS at 5 years was 16% and 20%, resp., with no significant differences between the induction groups. With a median follow up of 26 months (range, 5–77), 77 out of 118 complete responders have relapsed and 7 died while in CR. Patients with de novo AML had a significantly better OS than those with secondary AML (17 vs. 11 months, p<0.001). Unfavorable cytogenetics were associated with a poor median OS (7 vs. 15 months, p<0.001). Following mini-FlagIda I, collection of at least 2x10E6 CD34+ PBSC/kg was feasible in 35 of 67 pts in whom mobilization of CD34+ cells was monitored. Late consolidation with ASCT (n=19) was not superior to mini-FlagIda II (n=16, DFS 24 vs. 27 months). Conclusions: In this randomized study with elderly AML patients, G-CSF priming did not result in an increased CR rate and was associated with higher induction mortality, but OS was not influenced. We demonstrated feasibility of ASCT in patients up to the age of 70 years, which was not superior to chemotherapy consolidation.

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