Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.     

Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer

Tumor cells from five freshly isolated ovarian tumors and four established human ovarian carcinoma cell lines were analyzed for the production of the immunoinhibitory cytokine transforming growth factor-beta (TGF-β) before and after exposure to gamma irradiation and/or the cytokines TNF-α plus IFN-γ. All fresh tumors secreted high levels of TGF-β when compared to the levels produced by the established ovarian carcinoma cell lines. TGF-β produced by fresh tumors was significantly reduced after high doses of gamma irradiation (10,000 cGy). In contrast with the established cell lines, irradiation significantly increased TGF-β secretion. Exposure of fresh tumor cells to cytokines followed by irradiation caused significant reduction of TGF-β released when compared to the amount released after exposure to cytokines only. However, in the established cell lines, cytokines followed by irradiation again significantly increased TGF-β production. These data indicate that high doses of irradiation in fresh ovarian tumors, unlike established ovarian carcinoma cell lines, can significantly reduce the local production of this potent immunoinhibitory cytokine. This effect could work to further amplify weak immunological responses within the tumor. In addition, these findings indicate major differences between fresh tumor samples and established cell lines and warn against the sole use of continuous cell lines as models for tumors growingin vivo.     

Effect of exogenous surfactant on total respiratory system compliance

We measured total respiratory system compliance (Crs) before and after instilling 25 mg artificial surfactant in 1 ml saline down the endotracheal tube of preterm babies requiring resuscitation at birth, and compared results with data from 6 similar babies receiving saline only. Surfactant did not produce a significant improvement in Crs.     

Two year cumulative incidence of trunk abnormalities in a schoolpopulation in Rotterdam, The Netherlands

We conducted a study of the 2 year cumulative incidence of trunkabnormalities in a cohort of 3,071 11 year old children (1,621boys, 1,450 girls). The following data were recorded: height,weight, signs of puberty and menarche. Trunk abnormality wasassessed in the erect child (asymmetry of shoulders and waistline,imbalance of the trunk, scoliosis, lordosis, kyphosis, swaybackand flexibility) and by the forward bending test (FBT) (ribhump or lumbar prominence, persisting scoliosis, kyphosis anddeviant lateral aspect). A normal FBT both at baseline and atfollow-up was found in 84% of the boys and in 79% of the girls.The 2 year cumulative incidence of an abnormal FBT was 10% inboys and 13% in girls.