A dose-response analysis of lenograstim plus dexamethasone for neutrophil mobilization and collection |
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Authors: | Heuft Hans-Gert Goudeva Lilia Pulver Nicole Grigull Lorenz Schwella Nimrod Blasczyk Rainer |
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Affiliation: | Department of Transfusion Medicine, Hannover Medical School, Hannover, Germany. gert@mh-hannover.de |
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Abstract: | BACKGROUND: The objective was to evaluate the dose-response relationship of lenograstim plus dexamethasone for neutrophil mobilization and collection. STUDY DESIGN AND 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. |
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