Mobilized @entity1 peripheral blood progenitor cells are potential alternatives to bone marrow cells as targets for ex vivo gene transfer. We report the transduction efficiency of retroviral-mediated gene transfer into myeloid progenitors of peripheral blood progenitor cell (PBPC) harvests, mobilized by high-dose @entity786 and @entity2841 , compared with nonmobilized bone marrow (BM). Eleven PBPC samples were enriched for @entity2280 + cells, preincubated with @entity2772 (10 ng/ml), @entity650 (50 ng/ml), and 10% autologous plasma for 42 hr, and transduced over a 6-hr incubation with @entity2772 + @entity650 and a retroviral vector carrying the NeoR gene. NeoR-specific sequences were detected by polymerase chain reaction in 10 cell pellets (91%). Gene expression in CFU-GM colonies was found in nine transduced samples (82%), with a mean transduction efficiency of 5.2% (95% CI, 1.3-11.8%) CFU-GM per PBPC sample. In univariate analysis, a higher transduction efficiency into CFU-GM correlated significantly with a higher CFU-GM concentration in the @entity2280 +-enriched sample (p = 0.009), a shorter interval from diagnosis (p < 0.001), and fewer months of prior cytotoxic treatment (p = 0.001); correlation with younger age was of borderline statistical significance (p = 0.077). In multivariate analysis a shorter interval from diagnosis and, to a lesser degree, a higher CFU-GM concentration in the @entity2280 +-enriched sample were independent predictors of higher transduction efficiency. Twelve BM samples were similarly transduced; 11 pellets were PCR positive. CFU-GM NeoR gene expression was 4.2% (95% CI, 2.0-7.2%) CFU-GM per BM sample, which was not significantly different from the transduction efficiency into PBPC cells. No correlation was found between the transduction efficiency of CFU-GM in BM samples and CFU-GM concentration in the @entity2280 +-enriched sample, time from diagnosis, months of prior cytotoxic treatment, and/or @entity1 age. Our data suggest that the transduction efficiency ex vivo may be influenced by time from diagnosis, CFU-GM concentration in the sample, and possibly by the extent of prior cytotoxic administration.

The influence of XXXX -related factors on ex vivo retroviral-mediated gene transfer into mobilized peripheral blood myeloid progenitors.

@entity1 :: ('9606', 'Species') :: ['human', 'patient'] @entity650 :: ('3569', 'Gene') :: ['IL-6'] @entity786 :: ('MESH:D003520', 'Chemical') :: ['cyclophosphamide'] @entity2772 :: ('3562', 'Gene') :: ['IL-3'] @entity2280 :: ('947', 'Gene') :: ['CD34'] @entity2841 :: ('1437', 'Gene') :: ['GM-CSF']
@entity1 :: (9606,Species) :: ['patient']
