A dose-response analysis of lenograstim plus dexamethasone for neutrophil mobilization and collection.
BACKGROUND
The objective was to evaluate the dose-response relationship of lenograstim plus dexamethasone for neutrophil mobilization and collection.


METHODS
In a prospective study, 260 healthy volunteers received oral dexamethasone (8 mg) plus a single subcutaneous injection of glycosylated granulocyte-colony-stimulating factor (G-CSF; lenograstim) at medians of 1.5 (1.0-2.3) microg per kg (n = 43), 3 (2.4-4.1) microg per kg (n = 73), 6 (4.3-7.9) microg per kg (n = 123), and 12 (8.2-17.2) microg per kg (n = 21) and underwent neutrophil collections with a polymorphonucleated neutrophil (PMN) program. White blood cell (WBC) counts and PMN mobilization and collection results were compared, and the severity and clinical significance of donor adverse reactions were evaluated. Fifty-two neutropenic patients (29 children, 23 adults) underwent 271 neutrophil transfusions (GTXs) every other day to maintain WBC levels continuously above 0.5 x 10(9) per L.


RESULTS
Within the dose range 1.5, 3, and 6 microg per kg, each doubling step was associated with a 10 to 15 percent PMN increase in peripheral blood up to 32.8 (19.1-49.2) x 10(9) per L (6 microg/kg; p </= 0.00032) as well as in the neutrophil concentrate up to 79 (34-150) x 10(9) per U (6 microg/kg; p </= 0.00042). A further doubling to 12 microg per kg achieved neither better mobilization nor better apheresis results. The rate of clinically important adverse reactions increased already with the 6 microg per kg mobilization step. The GTX resulted in median peak WBC increments to 3.8 (0.4-18.2) x 10(9) per L (children) and 1.6 (0.3-9.4) x 10(9) per L (adults), but in adults the WBC threshold of 0.5 x 10(9) per L was not continuously exceeded.


CONCLUSIONS
The most effective dose-response ratio for PMN mobilization was demonstrated in the 6 microg per kg lenograstim group. In neutropenic adults, GTX treatment on an every-other-day schedule may be ineffective.
Heuft
Hans-Gert
HG
Department of Transfusion Medicine, Hannover Medical School, Hannover, Germany. gert@mh-hannover.de
Goudeva
Lilia
L
Pulver
Nicole
N
Grigull
Lorenz
L
Schwella
Nimrod
N
Blasczyk
Rainer
R
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D001782:Blood Donors; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007223:Infant; D000078224:Lenograstim; D007937:Leukapheresis / Q000379:methods*; D017708:Leukocyte Transfusion; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000628:therapy; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects
D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D003907:Dexamethasone