Delayed effects of rhG-CSF mobilization treatment and apheresis on circulating CD34+ and CD34+ Thy-1dim CD38- progenitor cells, and lymphoid subsets in normal stem cell donors for allogeneic transplantation.
Allogeneic transplantation of peripheral blood progenitor cells (PBPC) is emerging as a new stem cell transplant modality. Rather than undergoing general anesthesia for bone marrow harvest, normal blood stem cell donors are subjected to rhG-CSF mobilization treatment followed by single or multiple apheresis. Whereas the effects of cytokine treatment and apheresis on stem cell peripheralization and collection have been described, little is known about delayed effects of rhG-CSF treatment and apheresis on a normal hematopoietic system, and there are no long-term data that address safety issues. Ten normal, patient-related donors underwent a 3 or 4 day rhG-CSF (filgrastim) treatment (12 micrograms/kg/day) followed by single or tandem apheresis. We monitored peripheral blood (PB) cellularity including CD34+ and lymphoid subsets at baseline, during cytokine treatment, prior to apheresis, and at days 2, 4, 7, 30 and 100 post-apheresis. The PB progenitor cell concentration peak prior to apheresis was followed by a nadir by day 7 and normalized by day 30, with the exception of the most primitive CD34+ Thy-1dim CD38- progenitor subset that reached a nadir by day 30. Lymphoid subsets such as CD3, 4, 8, suppressor cells (CD3+ 4- 8- TCR+ alpha beta), and B cells (CD19+) showed a similar pattern with a nadir concentration by day 7, followed, except for B cells, by a rebound by day 30 and subnormal counts at day 100. The PB concentrations of hemoglobin and platelets dropped mainly due to the apheresis procedure itself, and normalized by day 30. With cytokine treatment, the PB alkaline phosphatase and lactate dehydrogenase concentrations increased 2.2- and 2.8-fold, respectively, over baseline, and returned to normal range by day 30. Based on the preliminary nature of this study, the clinical relevance of these findings is still unclear.
Körbling
M
M
University of Texas, MD Anderson Cancer Center, Division of Medicine, Houston 77030, USA.
Anderlini
P
P
Durett
A
A
Maadani
F
F
Bojko
P
P
Seong
D
D
Giralt
S
S
Khouri
I
I
Andersson
B
B
Mehra
R
R
vanBesien
K
K
Mirza
N
N
Przepiorka
D
D
Champlin
R
R
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000469:Alkaline Phosphatase / Q000097:blood; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001772:Blood Cell Count / Q000187:drug effects; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000187:drug effects*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007937:Leukapheresis / Q000009:adverse effects; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D010865:Pilot Projects; D011446:Prospective Studies; D011994:Recombinant Proteins; D018800:Thy-1 Antigens / Q000032:analysis; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D006454:Hemoglobins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D018800:Thy-1 Antigens; D016179:Granulocyte Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D000069585:Filgrastim