title: A dose-response analysis of lenograstim plus dexamethasone for neutrophil mobilization and collection.
abstract: 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.
authors.affiliation: Department of Transfusion Medicine, Hannover Medical School, Hannover, Germany. gert@mh-hannover.de
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Heuft
authors.forename: Lilia
authors.initials: L
authors.lastname: Goudeva
authors.forename: Nicole
authors.initials: N
authors.lastname: Pulver
authors.forename: Lorenz
authors.initials: L
authors.lastname: Grigull
authors.forename: Nimrod
authors.initials: N
authors.lastname: Schwella
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D003907:Dexamethasone