Immunological and clinical effects of post-transplant G-CSF versus placebo in T-cell replete allogeneic blood transplant patients: results from a randomized double-blind study.

BACKGROUND: Immunological and clinical effects of post-transplant growth factor administration have not been well studied. This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF (10 microg/kg) or placebo. METHODS: Immune status, including number of lymphocyte subsets and their functions, and serum immunoglobulin levels and clinical status--including GvHD, rate of relapse, event-free survival, and overall survival--were determined in the patients enrolled in this study. RESULTS: Twenty-eight patients survived 1 year after transplant, and 15 patients had available results to compare immune function by randomization assignment. At 12 months post-transplant, immune parameters in G-CSF versus placebo groups showed no statistically significant differences in number of circulating lymphocyte subsets CD3, CD4, CD8, CD19 and CD56 in the two groups. There was no significant (NS) difference in immunoglobulin IgG, IgA and IgM levels, NK or LAK cell-mediated cytotoxicity levels, and mitogen-induced proliferation between post-transplant G-CSF and placebo group. In addition, the analyses of immune parameters at earlier time-points on Days 28, 100, 180, and 270 revealed that, except for LAK cytotoxicity at Day 100, there was no differences between the two groups. Fourteen of 26 patients are alive in the G-CSF arm and nine of 24 in the placebo arm. Median follow-up of surviving patients is 43 months. Four year overall and event-free survival in the G-CSF and the placebo group were 53% and 35% (NS), and 44% and 36% (NS) respectively. Bacterial or fungal infections were the cause of six of 12 deaths in the G-CSF arm (all bacterial) and of four of 15 deaths in the placebo arm (two deaths from Aspergillus) (P=0.26). Two patients relapsed in the G-CSF arm and three in the placebo arm. Four year cumulative incidences of relapse were 8% versus 13% in G-CSF versus placebo arms, respectively, (NS). Chronic GvHD developed in 14 of 19 100-day survivors after G-CSF (11 extensive stage), and in 17 of 20 (14 extensive stage) in the placebo arm. The 4-year cumulative incidence of chronic GvHD was 56% [95% confidence interval (CI) 24-88%] after G-CSF and 71% (95% CI 48-94%) after placebo; this difference was not statistically significant (log rank P=0.41). CONCLUSION: In summary, there were no significant immunological or alterations in clinical benefit of post-transplant G-CSF administration in T-replete allotransplant recipients.

A comparison of root growth dynamics of silver maple and flowering dogwood in compacted soil at differing soil water contents.

Many bottomland tree species are tolerant of compacted soil and perform well in urban environments; however, the mechanism underlying this tolerance is unknown. Increased soil water content has been shown to alleviate some of the effects of soil compaction on plant growth, presumably because increasing soil water reduces soil strength. We hypothesized that tree species tolerant of very wet soils would have opportunities for root growth in compacted soil when high soil water contents reduced soil strength, whereas species intolerant of bottomland conditions would not. We tested this hypothesis on flowering dogwood (Cornus florida L.), a mesic species intolerant of inundation, and silver maple (Acer saccharinum L.), a bottomland species. Seedlings of both species were grown in pots for 21 and 30 days, respectively, in a growth chamber in native loam soil maintained at various combinations of soil strength and soil water tension. Downward root growth rate decreased in response to increasing soil strength in both species. At low soil strength (0.6 MPa), downward root growth rate of dogwood seedlings slowed when soil was either excessively wet or dry, whereas root growth rate of silver maple seedlings increased linearly with soil water content. In moderately compacted soil (1.5 g cm(-3) bulk density), silver maple seedlings had greater root growth rate, root length per plant, and ratio of root length to root dry weight in wet soil (0.006 MPa soil water tension) than in moist and dry soils (0.026 and 0.06 MPa, respectively), even though mean oxygen diffusion rate (ODR) was only 0.28 &mgr;g cm(-2) (SE = 0.05). No such effect was detected in highly compacted soil (1.7 g cm(-3) bulk density) in either species. Mean ODR showed a weak positive correlation with soil water tension (r = 0.40, P = 0.07), but was unrelated to soil strength. We conclude that silver maple roots can grow in moderately compacted soil when high soil water content decreases soil strength, whereas dogwood is unable to take advantage of this opportunity.