How much does dexamethasone increase the peripheral leukocyte count?

Dexamethasone-Induced Leukocytosis

Dexamethasone typically increases the white blood cell count by 2-4 fold (100-300% increase), with peak neutrophil elevation occurring 4-6 hours after administration, primarily through neutrophil demargination and mobilization from bone marrow reserves. 1

Magnitude and Timing of WBC Elevation

• Peak neutrophil count occurs 4-6 hours after oral or intravenous dexamethasone administration, with the increase almost entirely due to mature neutrophils 1
• A second, smaller rise in neutrophil count occurs at 24 hours after oral administration 1
• The dose-dependent effect is mediated through G-CSF elevation: low-dose dexamethasone (0.04 mg/kg) increases G-CSF by 240%, while high-dose (1.0 mg/kg) increases G-CSF by 871% at 24 hours 2
• The neutrophil increase persists for up to 24 hours in a dose-dependent manner 3

Mechanism and Cell-Specific Effects

Neutrophils increase while lymphocytes decrease, creating a characteristic pattern:

• Neutrophilia develops through decreased margination and mobilization from bone marrow pools, not through increased production 1, 2
• Lymphopenia occurs concomitantly with the initial neutrophil rise, followed by lymphocyte rebound at 24 hours 1, 3
• Monocytes, basophils, and eosinophils all decrease at 4 hours in a dose-dependent manner, with rebound increases at 24 hours 3
• All cell counts typically return to baseline by 7 days after a single dose 3

Dose-Response Relationship

The magnitude of leukocytosis is directly proportional to dexamethasone dose:

• Dexamethasone 4-8 mg/m² produces adequate neutrophilia with minimal discomfort in healthy volunteers 1
• There is a direct relationship between plasma dexamethasone concentration and neutrophil count rise following intravenous (but not oral) administration 1
• Higher cumulative doses intensify the lymphopenic effect, with dexamethasone being approximately 10 times more potent than hydrocortisone in inducing lymphopenia 4

Clinical Implications and Warnings

Dexamethasone-induced leukocytosis carries significant clinical consequences that must be monitored:

• In glioblastoma patients, dexamethasone-induced leukocytosis is associated with decreased overall survival (HR 2.25) and progression-free survival (HR 2.23) 5
• Grade ≥3 lymphopenia occurs in 25-63% of patients on dexamethasone-containing cancer regimens, requiring regular CBC monitoring 4
• High-dose dexamethasone regimens cause more severe toxicity than low-dose regimens, contributing to inferior survival through increased infections (pneumonia 16% vs 9%) 6, 4
• The lowest effective dexamethasone dose should be used, as low-dose regimens produce superior survival despite lower response rates 4

Common Pitfalls

• Do not interpret dexamethasone-induced leukocytosis as infection—the WBC elevation is expected and peaks at 4-6 hours 1
• Neutrophil alkaline phosphatase (NAP) activity falls as neutrophil count rises, which can help distinguish steroid-induced neutrophilia from infection 1
• The leukocytosis does not indicate increased immune function—paradoxically, it represents immunosuppression with increased infection risk, particularly pneumonia 6, 4
• Older patients are at higher risk for developing dexamethasone-induced leukocytosis 5