Changes in surrogate clinical end points.*
| . | . | Pretherapy . | Post-cycle 1 . | P† . | Post-cycle 2 . | P‡ . | Normal Range . | Multivariate Regression Analysis (P < 0.05) . |
|---|---|---|---|---|---|---|---|---|
| *Statistical analysis of changes in RBC adhesion to thrombospondin (TSP) and laminin, levels of D-dimers, Thrombin-antithrombin (TAT) complexes, prothrombin fragments 1 and 2 (F1+2), C-reactive protein (CRP), soluble VCAM (sVCAM) and von Willebrand factor propeptide (VWFpp). The variables that changed significantly with treatment were analyzed for correlations with the following hematological parameters: percentage F cells, absolute neutrophil counts, total hemoglobin, and reticulocyte counts (multivariate regression analysis); significant associations are shown in the last column. | ||||||||
| Values are mean ± SE; paired 2-tailed t test. | ||||||||
| † P, significance of change from pretherapy to postcycle 1. | ||||||||
| ‡ P, change from pretherapy to postcycle 2. | ||||||||
| Measures of RBC adhesion to endothelium | Adhesion to TSP (RBCs/mm2) | 1570 ± 170 | 690 ± 150 | < 0.001 | 910 ± 160 | < 0.001 | < 60 | F cell % and ANC |
| Adhesion to laminin (RBCs/mm2) | 3470 ± 500 | 1950 ± 300 | 0.004 | 1570 ± 210 | < 0.001 | < 250 | F cell % | |
| Measures of thrombin generation and fibrinolysis | D-dimer (ng/mL) | 490 ± 90 | 320 ± 50 | 0.02 | 300 ± 50 | 0.03 | < 400 | Nil |
| TAT (ug/L) | 7.0 ± 1.7 | 8.6 ± 2.3 | 0.15 | 5.2 ± 0.9 | 0.11 | 1.0 – 4.1 | ||
| F1+2 (nmol/L) | 1.75 ± 0.22 | 1.56 ± 0.16 | 0.23 | 1.41 ± 0.15 | 0.051 | 0.04–1.1 | ||
| Measure of inflammation | CRP (mg/dL) | 1.25 ± 0.27 | 1.19 ± 0.34 | 0.80 | 0.82 ± 0.26 | 0.18 | < 0.7 | |
| Measures of endothelial cell damage | sVCAM (ng/mL) | 1170 ± 140 | 930 ± 100 | 0.01 | 840 ± 100 | 0.02 | 395–714 | Total Hb |
| VWFpp (u/dL) | 196 ± 26 | 156 ± 28 | 0.015 | 144 ± 13 | 0.049 | 74–153 | Absolute reticulocyte count | |
| . | . | Pretherapy . | Post-cycle 1 . | P† . | Post-cycle 2 . | P‡ . | Normal Range . | Multivariate Regression Analysis (P < 0.05) . |
|---|---|---|---|---|---|---|---|---|
| *Statistical analysis of changes in RBC adhesion to thrombospondin (TSP) and laminin, levels of D-dimers, Thrombin-antithrombin (TAT) complexes, prothrombin fragments 1 and 2 (F1+2), C-reactive protein (CRP), soluble VCAM (sVCAM) and von Willebrand factor propeptide (VWFpp). The variables that changed significantly with treatment were analyzed for correlations with the following hematological parameters: percentage F cells, absolute neutrophil counts, total hemoglobin, and reticulocyte counts (multivariate regression analysis); significant associations are shown in the last column. | ||||||||
| Values are mean ± SE; paired 2-tailed t test. | ||||||||
| † P, significance of change from pretherapy to postcycle 1. | ||||||||
| ‡ P, change from pretherapy to postcycle 2. | ||||||||
| Measures of RBC adhesion to endothelium | Adhesion to TSP (RBCs/mm2) | 1570 ± 170 | 690 ± 150 | < 0.001 | 910 ± 160 | < 0.001 | < 60 | F cell % and ANC |
| Adhesion to laminin (RBCs/mm2) | 3470 ± 500 | 1950 ± 300 | 0.004 | 1570 ± 210 | < 0.001 | < 250 | F cell % | |
| Measures of thrombin generation and fibrinolysis | D-dimer (ng/mL) | 490 ± 90 | 320 ± 50 | 0.02 | 300 ± 50 | 0.03 | < 400 | Nil |
| TAT (ug/L) | 7.0 ± 1.7 | 8.6 ± 2.3 | 0.15 | 5.2 ± 0.9 | 0.11 | 1.0 – 4.1 | ||
| F1+2 (nmol/L) | 1.75 ± 0.22 | 1.56 ± 0.16 | 0.23 | 1.41 ± 0.15 | 0.051 | 0.04–1.1 | ||
| Measure of inflammation | CRP (mg/dL) | 1.25 ± 0.27 | 1.19 ± 0.34 | 0.80 | 0.82 ± 0.26 | 0.18 | < 0.7 | |
| Measures of endothelial cell damage | sVCAM (ng/mL) | 1170 ± 140 | 930 ± 100 | 0.01 | 840 ± 100 | 0.02 | 395–714 | Total Hb |
| VWFpp (u/dL) | 196 ± 26 | 156 ± 28 | 0.015 | 144 ± 13 | 0.049 | 74–153 | Absolute reticulocyte count | |