Recombinant human interleukin-3 (rhIL-3) enhances the mobilization of peripheral blood progenitor cells by recombinant human granulocyte colony-stimulating factor (rhG-CSF) in normal volunteers.
To identify a precisely timed and safe protocol for progenitor cell mobilization, we studied the effects of rhIL-3 and rhG-CSF administration to normal volunteers. rhG-CSF 5 micrograms/kg/d was administered subcutaneously (s.c.) for 7 consecutive days either alone or preceded by rhIL-3 5 micrograms/kg/d s.c. for 4 consecutive days in sequential or partially overlapping schedules. The combined cytokines were well-tolerated--adverse effects were similar to those of the individual agents. Total white blood cell (WBC) and neutrophil counts rose briskly in response to rhG-CSF, and peak mean values were similar between treatment cohorts. Mean platelet counts were modestly elevated during rhG-CSF treatment only in the cohorts receiving rhIL-3 and rhG-CSF. Mean circulating CD34+ cells peaked on day 5 in the rhG-CSF group (38.9+/-14.3/microliter), day 6 in the sequential rhIL-3/rhG-CSF group (56.4+/-12.4/microliter), and day 6 in the partial overlap group (46.1+/-10.9/microliter). On day 3, mean CD34+ cell counts of the subjects who received sequential treatment were markedly higher than observed in the other groups (p<0.05) and were estimated to have been sufficient for collection of adequate grafts by single 10-L leukapheresis procedures in 60% of subjects. Circulating clonogenic cells (CFU-GM and/or BFU-E) were substantially higher in the sequential group than the rhG-CSF group on days 3-6 but were only minimally elevated above baseline in the partial overlap group. The numbers of circulating CD34+/Lin-/Thy-1+ cells (putative stem cells) were increased substantially, especially in the sequential group. On the basis of this pilot trial, we conclude that priming with rhIL-3 is a safe and well-tolerated method for enhancing the mobilization of human blood progenitors and stem cells by rhG-CSF.
Huhn
R D
RD
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Yurkow
E J
EJ
Tushinski
R
R
Clarke
L
L
Sturgill
M G
MG
Hoffman
R
R
Sheay
W
W
Cody
R
R
Philipp
C
C
Resta
D
D
George
M
M
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007937:Leukapheresis; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D012449:Safety; D018800:Thy-1 Antigens / Q000032:analysis
D018952:Antigens, CD34; D007377:Interleukin-3; D011994:Recombinant Proteins; D018800:Thy-1 Antigens; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim