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Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model
Published on: August 29, 2012
Administration of G--CSF plus dexamethasone produces greater granulocyte concentrate yields while causing no more
D F Stroncek1, Y Y Yau, J Oblitas
1Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. dstroncek@dtm.cc.nih.gov
Insights
Granulocyte-colony stimulating factor (G-CSF) plus dexamethasone maximizes granulocyte yields for transfusion. Sequential collections are safe after 7 days, with 4 weeks recommended for regular donors.
Area of Science:
- Hematology
- Transfusion Medicine
- Pharmacology
Background:
- Granulocyte-colony stimulating factor (G-CSF) and dexamethasone are standard agents for mobilizing granulocytes.
- Optimizing collection yields and donor safety is crucial for transfusion efficacy.
Purpose of the Study:
- To evaluate if toxicities of G-CSF with or without dexamethasone are offset by increased collection yields.
- To determine the minimum interval for safe sequential granulocyte collections.
Main Methods:
- Twenty donors received either dexamethasone alone, G-CSF alone, or G-CSF plus dexamethasone.
- Granulocytes were collected via apheresis.
- Donor symptoms, cell counts, and blood chemistries were monitored post-collection.
Main Results:
- G-CSF plus dexamethasone yielded significantly more granulocytes (67.1 x 10^9) compared to G-CSF (41.1 x 10^9) or dexamethasone alone (21.0 x 10^9).
- Donor symptoms were reported in 58-85% of participants across regimens.
- Platelet counts decreased post-collection, with mild granulocytopenia observed at 21 days.
Conclusions:
- G-CSF plus dexamethasone is supported for granulocyte donors due to superior yields.
- Donor toxicities and hematological changes were similar across regimens.
- Safe sequential collections are possible after 7 days, with 4 weeks recommended for regular donors.
Background:
G-CSF with or without dexamethasone is becoming the standard agent for mobilizing granulocytes for transfusion. The purpose of this study was to determine if the toxicities of G--CSF with or without dexamethasone are offset by greater collection yields and to define the minimum interval that should separate sequential collections.
Study Design And Methods:
Twenty donors were studied on three occasions. They were given either dexamethasone (8 mg, by mouth) plus a placebo injection, G--CSF (5 microg/kg, given subcutaneously) plus placebo capsules, or G--CSF plus dexamethasone. Granulocytes were collected by apheresis. A donor symptom survey was administered, and cell counts and blood chemistries were assessed before collection and 1, 2, 7, 14, 21, 28, and 35 days after collection.
Results:
More granulocytes were collected when G--CSF was given than when dexamethasone was given (41.1 +/- 20.4 x 10(9) vs. 21.0 +/- 10.0 x 10(9); p<0.001), but the use of G--CSF plus dexamethasone produced the greatest yields (67.1 +/- 22.0 x 10(9); p<0.002). When the donors were given dexamethasone alone, 58 percent experienced at least one symptom, compared to 85 percent of those given G--CSF and 75 percent of those given G--CSF plus dexamethasone. In all three regimens, platelet counts fell 19 percent to 24 percent after collection and remained below baseline for 7 to 14 days. Granulocyte counts returned to baseline within 3 to 7 days, but, in all three regimens, a mild granulocytopenia occurred 21 days after collection. With each of the regimens, blood chemistries changed, but the changes were mild and most returned to baseline within 7 days; however, changes in albumin, bilirubin, and AST persisted until 28 days after collection.
Conclusion:
These results support the use of G--CSF plus dexamethasone in granulocyte donors. G--CSF plus dexamethasone resulted in greater granulocyte yields than either agent alone and was associated with donor symptoms and changes in blood cell counts and chemistries similar to those seen with G--CSF alone or dexamethasone alone. Granulocytes can be safely collected a second time after a 7-day interval; however, for regular donors, it may be best to separate collections by 4 weeks.
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