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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone-marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral-blood progenitor cells and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. 17 patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone-marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral-blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days after infusion of haemopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. This method may be widely applicable to aid both neutrophil and platelet recovery after high-dose chemotherapy; it will allow investigation of peripheral-blood progenitor-cell allotransplantation.
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PMID:Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. 137 71

This report summarizes our results of sequential treatment with IL-3 and GM-CSF following high-dose chemotherapy with respect to the yield and composition of peripheral blood stem cells (PBSC). Eight patients with high-grade non-Hodgkin's lymphoma were included in the study. Starting 24 h after high-dose cytosine arabinoside (Ara C)/mitoxantrone, IL-3 was given for 6 days, followed by GM-CSF. The increase of circulating hematopoietic progenitor cells during leukocyte recovery varied substantially from patient to patient. Up to a 22-fold interindividual difference was observed for the peak levels of CD34+ cells. A special focus of our study was the antigenic profile of the CD34+ PBSC. On analysis of the antigenic profile of the CD34+ cells, the proportion of CD34+/HLA-DR- and CD34+/CD38- cells representing non-committed hematopoietic stem cells was consistently < 5%. The vast majority of CD34+ cells was found to coexpress CD33 (86.3 +/- 2.1%, mean +/- SEM), reflecting myeloid lineage commitment. CD71 antigen was present on 47.4 +/- 3.0% CD34+ cells with two populations (CD71dim/bright), while the percentage of early B lymphoid (CD34+/CD19+) progenitor cells was extremely low (0.38 +/- 0.13%). We therefore conclude that the cytokines currently available such as G-CSF, GM-CSF or IL-3 facilitate an ontogenetic phenomenon supporting the redistribution of hematopoietic progenitor cells after cytotoxic treatment. Six patients were autografted with the IL-3/GM-CSF-exposed blood stem cells following high-dose conditioning therapy. It is worth noting that no additional BM or hematopoietic growth factors were given post-transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autografting with peripheral blood stem cells mobilized by sequential interleukin-3/granulocyte-macrophage colony-stimulating factor following high-dose chemotherapy in non-Hodgkin's lymphoma. 751 Oct 17

It was the objective of the study to characterize CD34+ hematopoietic progenitor cells from peripheral blood (PB) and bone marrow (BM) in a group of 24 cancer patients. After cytotoxic chemotherapy, R-metHu granulocyte colony-stimulating factor (R-metHuG-CSF; filgrastim, 300 micrograms daily, subcutaneously) was given to shorten the time of neutropenia as well as to increase the rebound of peripheral blood progenitor cells (PBPC) for harvesting. The proportion of CD34+ cells in the leukapheresis products (LPs) was 1.4-fold greater than in BM samples that were obtained at the same day (LP: median, 1.4% v BM: median, 1.0%, P < .01). Two- and three-color immunofluorescence showed that blood-derived CD34+ cells comprised a greater proportion of a particular early progenitor cell than CD34+ cells of bone marrow. Blood-derived progenitor cells tended to have a higher mean fluorescence intensity of CD34 and expressed significantly lower levels of HLA-DR (mean fluorescence intensity of HLA-DR: 442.6 +/- 44.9 [LP] v 661.5 +/- 64.6 [BM], mean +/- SEM, P < .01). Furthermore, the blood-derived CD34+ cells comprised a 1.7-fold greater proportion of Thy-1+ cells (LP: median, 24.4% v BM: median, 14.4%, P < .001) and expressed significantly less c-kit (LP: median, 20.5% v BM: median, 31.0%, P < .01). Three-color analysis showed that high levels of Thy-1 expression were restricted to CD34+/HLA-DRdim or CD34+/HLA-DR- cells confirming the early developmental stage of this progenitor cell subset. The proportion of CD34+/CD45RA(bright) cells representing late colony-forming unit granulocyte-macrophage (CFU-GM) was smaller in LPs compared with BM (P < .05). For an examination of BM CD34+ cells before the mobilization chemotherapy, samples of 16 patients were available. The mean proportion of c-kit expressing CD34+ cells in the bone marrow during G-CSF-stimulated reconstitution decreased 1.8-fold compared with baseline values. There was no difference in the proportion of BM-derived CD34+/Thy-1+ cells and CD34+/CD45RA+ cells between steady-state hematopoiesis and G-CSF-supported recovery. Our data suggest that during G-CSF-enhanced recovery, CD34+ cells in the PB are enriched with more primitive progenitor cells to evenly replenish the BM after the chemotherapy-related cytotoxic damage.
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PMID:Blood-derived autografts collected during granulocyte colony-stimulating factor-enhanced recovery are enriched with early Thy-1+ hematopoietic progenitor cells. 753 95

Peripheral blood progenitor cells (PBPC) were mobilised by recombinant human G-CSF (rhG-CSF) and cyclophosphamide, harvested by apheresis from 9 patients with NHL and stored at 4 degrees C without further manipulation. They were then reinfused after high-dose chemotherapy. We monitored the change in colony-forming units-granulocyte, macrophage (CFU-GM) proliferation as well as plasma glucose, lactate and pH levels over the period of the study. In an attempt to maintain CFU-GM numbers, rhG-CSF was added to storage bags at collection and 48 h later. Our observations suggest that cell viability is well maintained and that CFU-GM numbers rise over the first 48 h of storage before falling rapidly. Metabolic changes cause a fall in the pH and glucose levels with a reciprocal rise in plasma lactate. The addition of rhG-CSF at a concentration of 10 ng/ml to cells in storage showed no detectable benefit. Following storage for 96 h, 77% (SEM +/- 8%) of the initial CFU-GM remained.
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PMID:Liquid storage of peripheral blood progenitor cells for transplantation. 753 74

The haematopoietic growth factor (HGF), granulocyte colony stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral blood progenitor cells (PBPC) and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. Seventeen patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for six days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leukapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral blood progenitors; the platelet count reached 50 x 10(9)/L a median of 15 days after infusion of haematopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. Subsequently, 10 patients received filgrastim-mobilised PBPC without marrow after high-dose chemotherapy. The rate of platelet and neutrophil recovery in these patients was at least equal to that observed in the patients receiving PBPC and bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of peripheral blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. 833 35

Insulin (I) plays a crucial role in the maturation of the perinatal brain, and it may also be involved in the pathogenesis of neonatal brain injuries. The aim of the present study was to reveal the effect of neonatal asphyxia on the regulation of I and glucose (G) metabolism in plasma and cerebrospinal fluid (CSF) in newborn piglets. The I concentrations were measured by radioimmunoassay, while the G levels were analyzed by the G oxidase method during three phases (basal, critical, recovery) of bilateral pneumothorax in newborn piglets. We observed a significant hyperinsulinism (p < 0.001) both in plasma and CSF and a mild hypoglycemia (p < 0.05) during the recovery period. Postasphyxial G infusion (1.1 M, 10 ml.kg-1) amplified the hyperinsulinism. The ICSF/plasma ratio (mean +/- SEM; n = 16) was decreasing during cardiovascular failure (0.09 +/- 0.02; NS) as compared with the initial value (0.12 +/- 0.04), then it returned to basal values by 60 min (0.14 +/- 0.04; NS), and increased significantly 180 min (0.40 +/- 0.14; p < 0.05) after resuscitation of the piglets. There was a similar increase in GCSF/plasma ratio in asphyxiated animals at the end of experiments (0.99 +/- 0.15 vs. initial 0.76 +/- 0.05; p < 0.05). In conclusion, neonatal asphyxia resulted in plasma and CSF hyperinsulinism which may alter hypoxic-ischemic cerebral damages.
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PMID:Plasma and cerebrospinal fluid hyperinsulinism in asphyxiated piglets. 895 16

The effect of different expansion protocols on the expression levels of CD49dw/CD29 (VLA-4), CD11a/CD18 (LFA-1), CD31 (PECAM-1), CD44, and CD34 was determined after cord blood CD34+ cells were cultured for defined periods with the following: 1) A growth factor mix (GFmix) containing interleukin (IL)-1, IL-3, IL-6, kit ligand (KL), G-CSF, GM-CSF, and erythropoietin (Epo); 2) IL-3 + KL; and 3) HS-5 (a human stromal cell line supernatant) + KL. Before culturing, cord blood CD34+ cells (> 95% purity) were 94 +/- 5% CD31+, 98 +/- 1% CD44+, 66 +/- 29% VLA-4+, and 68 +/- 18% LFA-1+ (mean +/- SEM). Immunophenotyping and morphological examination of pre- and post-cultured cells indicated that GFmix preferentially supported erythroid development, while IL-3+KL and HS-5+KL preferentially supported myeloid development. Similar to what other investigators have reported, there was an absolute increase in CD34+ cell numbers as well as clonogenic precursors with ex vivo expansion. However, the majority of clonogenic precursors post-expansion expressed CD34 antigen at reduced levels. Examination of adhesion molecules indicated that a majority of cells cultured with GFmix expressed PECAM-1 and LFA-1 at undetectable levels, but PECAM-1 and LFA-1 levels remained essentially unchanged when cells were cultured with IL-3+KL and HS-5+KL. Overall VLA-4 expression levels slightly increased and CD44 expression levels were more heterogeneous with ex vivo expansion. Nevertheless, LFA-1, VLA-4, PECAM-1, and CD44 expression levels remained essentially unchanged on cultured progeny retaining a CD34 phenotype, independent of the culture system used. Together these results indicate that differential modulation of adhesion markers occur with different culture conditions, yet adhesion receptor expression levels on progeny cells retaining a CD34 phenotype are essentially maintained independent of the culture conditions. And although there is an absolute increase in CD34+ cells after ex vivo expansion, a majority of clonogenic precursors have reduced levels of CD34 antigen.
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PMID:Differential modulation of adhesion markers with ex vivo expansion of human umbilical CD34+ progenitor cells. 931 Jan 90

In synergy with the CD4 antigen, the chemokine receptor CXCR-4 functions as a coreceptor for T-cell-tropic HIV-1 strains. Using two- and three-color immunofluorescence analysis, we examined the expression of CXCR-4 on CD34+ cells in 21 samples obtained from leukapheresis (LP) products of cancer patients who underwent G-CSF-supported cytotoxic chemotherapy. In addition, eight samples from bone marrow (BM) were obtained. CXCR-4 was expressed on the surface of CD34+ cells from samples of both hematopoietic sources. The mean proportion of CD34+/CXCR-4+ cells from LP products was 1.7-fold greater in comparison with those from bone marrow (65.9+/-4.1% vs. 37.5+/-8.6% [+/- SEM], p < 0.05). For an intraindividual comparison, LP products and bone marrow from six patients were obtained on the same day, confirming the significantly greater proportion of CD34+ cells coexpressing CXCR-4 cells in LP products. In order to examine whether the CXCR-4 expression was related to the stage of maturation and differentiation of CD34+ cells, six samples from LP products and four samples from bone marrow were assessed using three-color immunofluorescence analysis. We found that the subset of CD34+/CD38low and CD34+/HLA-DRlow cells representing a population of more immature progenitor cells were brightly positive for CXCR-4, while there was a decrease in the level of CXCR-4 expression in the population of CD34+/HLA-DRbright and CD34+/CD38bright cells. Based on the assessment of ten LP products, we found that the mean proportion of CD34+ cells coexpressing CD4 and CXCR-4 was 6.2+/-2.3% [+/- SEM], suggesting that a small population of CD34+ cells are, in principle, susceptible for an infection with T-cell-tropic HIV-1 strains. In conclusion, our data suggest that CXCR-4 is present on the surface of hematopoietic progenitor cells--particularly more primitive CD34+ cells. CXCR-4 could play a role in the homing of CD34+ cells to stromal elements of the bone marrow via its natural ligand stromal-derived factor-1 (SDF-1).
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PMID:The human immunodeficiency virus (HIV)-type 1 coreceptor CXCR-4 (fusin) is preferentially expressed on the more immature CD34+ hematopoietic stem cells. 985 43

To identify the optimal time for the collection of CD56(+) cytotoxic lymphocytes for adoptive immunotherapy in patients undergoing high-dose chemotherapy (HDCT) and peripheral blood stem cell (PBSC) transplantation, 18 breast cancer patients receiving either three cycles of epirubicin/paclitaxel (CT x 3) followed by HDCT and PBSC transplantation (n = 12) or CTx6 (n = 6) were studied. Blood samples were obtained before each CT/HDCT cycle, from PBSC collections, and repeatedly after autografting for up to 12 months. The number of CD56(+)3(-) and CD56(+)3(+) lymphocytes, their in vitro expandability with interleukin-2, and their cytotoxicity against MCF-7 and Daudi cells were analyzed. Six healthy females served as controls. CD56(+) cell counts in both treatment groups were subnormal but stable during the observation period. The cytotoxicity of the expanded CD56(+) cells was normal and unaffected by the treatment. The in vitro CD56(+) cell expandability (controls, 100 +/- 31-fold, mean +/- SEM) was normal before CT1 and CT2, but reduced in PBSC harvests performed after CT2 and application of G-CSF (21 +/- 6-fold; p < 0.01). After PBSC harvesting, the CD56(+) cell expandability increased to 185 +/- 74-fold and 170 +/- 69-fold (before CT3 and HDCT). This increase was not observed in those patients who did not undergo PBSC mobilization. Two weeks after autografting, the CD56(+) cell expandability was minimal (6 +/- 1-fold), and recovered to 34 +/- 6-fold. Thus, CT, HDCT and autografting do not alter the frequency and inducible cytotoxicity of CD56(+) cells in breast cancer patients. However, the proliferative capacity of CD56(+) cells obtained from PBSC harvests and after autografting is impaired. Therefore, instead of the PBSC graft, maximally expandable CD56(+) cells obtained at least 1 week after PBSC collection should be considered for adoptive immunotherapy after PBSC autografting.
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PMID:Optimal timing for the collection and in vitro expansion of cytotoxic CD56(+) lymphocytes from patients undergoing autologous peripheral blood stem cell transplantation. 1152 34

The pathophysiology of preeclampsia (PET) implicates an inflammatory dysfunction. This study profiled this host response by challenging whole blood with lipopolysaccharide. Multiplex immunoassays determined interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, granulocyte/granulocyte macrophage-colony stimulating factors (G-CSF/GM-SCF), interferon(IFN)-gamma, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein-1beta and tumor necrosis factor (TNF)-alpha levels. Secretory capacity was expressed in pg/million white cells or monocytes (+/-SEM). PET featured significantly higher IL-1beta, IL-2, IL-10, IL-13, G-CSF, IFN-gamma, MCP-1 and TNF-alpha monocyte secretory capacities (p < 0.05). The PET group exhibited an inflammatory hyper-responsiveness (p < 0.01) which was poorly described by the traditional Th1:Th2 dichotomy.
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PMID:Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model. 1829


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