Mobilization of peripheral blood progenitor cells for human immunodeficiency virus-infected individuals

Gene therapy is becoming one of the most promising modalities for the treat ment of acquired immunodeficiency syndrome. The purpose of this study was t o investigate the mobilization and collection of peripheral blood progenito r cells from human immunodeficiency virus (HIV)-infected individuals using granulocyte colony-stimulating factor (G-CSF), A total of 10 patients (9 ma le, I female; median age 36.5 years) with varying circulating CD4(+) cell c ounts (13.9-1467/mu L) were administered 10 mu g/kg G-CSF daily for 6 days. Peripheral white blood cells (WBCs), CD34(+) cell counts, lymphocyte subse ts, and plasma viremia were monitored before each G-CSF injection. An avera ge sixfold increase in WBCs was observed, which stabilized on day 4 or ther eafter. The level of CD34(+) cells was increased by 20-fold, and did not di ffer between days 5 and 6, Smaller increases in CD4(+), CD8(+), and CD4(+)C D8(+) cells were observed. HIV viral load, as measured by RNA copy number i n plasma, was not significantly altered by G-CSF administration. The leukap heresis product (LP), collected on day 7, contained an average of 6.25 +/- 4.52 (mean +/- standard deviation) X 10(10) WBCs and 3.08 +/- 2.98 X 10(6) CD34(+) cells/kg, The levels of different CD34(+) cell subsets were similar to those in the LPs of G-CSF-mobilized healthy individuals from an earlier study. Primitive hematopoietic cells (CD38(-) and CD38(-)HLA-DR+ cells) we re detected in LPs (1.19 +/- 0.46% and 0.87 +/- 0.23%, respectively, of CD3 4(+) cells). All parameters (WBC counts, lymphocyte populations, CD34(+) ce lls, and HIV-1 RNA copies) measured 3 weeks after leukapheresis returned to baseline values. The administration of G-CSF was well tolerated by the HIV patients; side effects included bone pain, headache, flu-like symptoms, an d fatigue. There were no correlations between baseline CD4(+) cell count an d the WBCs, mononuclear cells, or CD34(+) cells collected in the LP, Simila rly, no correlation existed between baseline CD4(+) and CD34(+) cells, peak CD34(+) cells, or days to achieve peak CD34(+) cell counts after G-CSF mob ilization, Our results showed that: (1) maximal mobilization can be achieve d after 4 days of G-CSF administration; (2) therapeutic quantities of hemat opoietic cells can be collected and used for gene therapy; and (3) G-CSF ad ministration is well tolerated and does not cause a clinically significant increase in viremina (C) 1999 International Society for Experimental Hemato logy. Published by Elseveir Science Inc.