Dose-dependent mobilisation of haematopoietic progenitor cells in healthy volunteers receiving glycosylated rHuG-CSF.
In an attempt to optimise the dose of G-CSF for mobilisation of PBPC in allogeneic donors, four groups of six healthy male volunteers received lenograstim (glycosylated rHuG-CSF) at a dose of 3, 5, 7.5 or 10 micrograms/kg/day, respectively, for 6 days (days 1-6). All subjects underwent a 10 I leukapheresis. Lenograstim was well tolerated. Maximal mobilisation was observed on days 5 or 6, with a clear dose-response for all progenitor cell types (CD34+, CFU-GM, BFU-E, CFU-mix). The peak numbers of CD34+ cells/microlitre (mean, s.e.m.) were 30 +/- 5, 49 +/- 8, 44 +/- 5 and 122 +/- 30 in the 3, 5, 7.5 and 10 micrograms/kg groups, respectively. A good correlation was observed between the number of CD34+ cells in blood and leukapheresis product (LP), respectively. Increasing the dose of lenograstim did not increase the number of T cells in the LP. A comparison of LP and steady state BM CD34+ cells in paired samples from each individual, showed a higher proportion of primitive immunophenotypes (CDw90+, HLA-DR-, CD45RA-, CD33-) among LP CD34+ cells. We conclude that increased doses of G-CSF improve the mobilisation of PBPC, and that G-CSF favours mobilisation of primitive CD34+ cell subsets. Lenograstim 10 micrograms/kg/day for 6 days should provide a sufficiently effective mobilisation of PBPC in most healthy PBPC donors.
Höglund
M
M
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Smedmyr
B
B
Simonsson
B
B
Tötterman
T
T
Bengtsson
M
M
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D006031:Glycosylation; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000187:drug effects*; D006801:Humans; D016130:Immunophenotyping; D000078224:Lenograstim; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D010865:Pilot Projects; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D012449:Safety; D063268:Sialic Acid Binding Ig-like Lectin 3; D018800:Thy-1 Antigens / Q000032:analysis
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D018800:Thy-1 Antigens; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D017493:Leukocyte Common Antigens