Mobilization of CD34+ progenitor cells by granulocyte colony-stimulating factor in human immunodeficiency virus type 1-infected adults.
We conducted a clinical trial to determine the feasibility of growth factor mobilization of CD34+ progenitor cells in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Eight asymptomatic, HIV-1-infected adults (median CD4+ T-cell count, 415 cells/microL), received 480 micrograms/d of granulocyte colony-stimulating factor (G-CSF) for 6 days without evidence of viral activation. Despite concerns that HIV-1 might inhibit hematopoiesis, CD34+ cells were successfully mobilized to the periphery of all donors, independent of the baseline CD4+ T-cell count, and the status of antiretroviral therapy. Leukapheresis was performed on day 6, and yielded a median of 194 x 10(6) CD34+ cells per leukapheresis (n = 7). CD34-enriched cells from the leukapheresis were predominantly myeloid-committed, but between 0.2% and 1.7% were primitive CD34+/CD38- progenitors. A median of 21.7% of the mobilized CD34+ cells were dimly positive for CD4. Consequently, CD34(+)-enriched cells were purified on the cell sorter (mean purity, 97.7% +/- 2.4%; n = 7), and examined for HIV-1 DNA. Purified CD34+ cells from two of seven donors were polymerase chain reaction (PCR)-positive for HIV-1, but only from one of three samples from each donor. We conclude that G-CSF can safely mobilize CD34+ progenitor cells in HIV-1-infected subjects, and that these cells are suitable for consideration in gene-transfer strategies.
Slobod
K S
KS
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Bennett
T A
TA
Freiden
P J
PJ
Kechli
A M
AM
Howlett
N
N
Flynn
P M
PM
Head
D R
DR
Srivastava
D K
DK
Boyett
J M
JM
Brenner
M K
MK
Garcia
J V
JV
D000328:Adult; D018952:Antigens, CD34; D002452:Cell Count / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D015497:HIV-1; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007937:Leukapheresis; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage
D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor