SEARCH · PubMed Health

Results for “Mobility”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources

PubMed2006

The mobilization of hematopoietic progenitors to peripheral blood is predictive of the hematopoietic syndrome after total or partial body irradiation of mice.

PURPOSE: In previous studies we showed that administration of mobilizing growth factors (MGFs) to mice previously exposed to total body irradiation mobilizes to peripheral blood (PB) a number of progenitors that correlates with the total reserve of progenitors surviving the exposure. Now we have tested whether this finding is independent of the radiosensitivity of the mice and of the homogeneity of the radiation exposure. Also we have investigated whether numbers of mobilized progenitors predict the hematopoietic syndrome after irradiation. METHODS AND MATERIALS: Mice were subjected to partial or total body irradiation and treated with MGFs. Thereafter, the number of colony-forming units granulocyte-macrophage progenitors in PB was correlated with the total reserve of surviving progenitors and with the nadir of leukocytes after the irradiation. RESULTS: The number of progenitors mobilized to PB after irradiation of normal and radiosensitive mice showed the same correlation with respect to the reserve of bone marrow progenitors surviving the exposure. Additionally, the number of mobilized progenitors correlated with the leukocytes' nadir after the irradiation, regardless of homogeneous or inhomogeneous exposures. CONCLUSIONS: In a mouse experimental model, the number of hematopoietic progenitors mobilized to PB by MGFs is a good predictor of the hematopoietic syndrome occurring after total or partial body irradiation.

Animals↗

PubMed2006

Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease.

BACKGROUND/AIMS: To evaluate feasibility, safety and pattern of bone marrow-derived cells (BMC) mobilization in patients with end stage liver cirrhosis following granulocyte-colony stimulating factor (G-CSF) administration. METHODS: Eight patients with severe liver cirrhosis (Child-Pugh score B-C, spleen diameter less than 170 mm) were included. They were treated with G-CSF (5 microg/kg b.i.d for three consecutive days) to mobilize BMC, evaluated as circulating CD34+ve cells (flow cytometry) and myeloid CFU-GM progenitors (in vitro colony growth assay). Co-expression in CD34+ve cells markers of differentiation (Thy1, CD133, CXCR4, c1qRp) were investigated on CD34+ve cells by double direct immunofluorescence. Data from 40 healthy haematopoietic stem cell donors were used as controls. RESULTS: Mobilization of CD34+ve cells occurred in all patients. It was paralleled by expansion of circulating CFU-GM progenitors. Circulating CD34+ve cells co-expressed epithelial and stem cell markers in both cirrhotics and volunteer stem cell donors. G-CSF was well tolerated, no adverse event occurred, a significant reversible increase of splenic longitudinal diameter was observed. CONCLUSIONS: (i) G-CSF mobilization of BMC co-expressing epithelial and stem markers occurred in all cirrhotic patients; (ii) splenomegaly up to 170 mm does not prevent safe BMC mobilization following G-CSF in patients with end stage liver disease; (iii) mobilized BMC may represent an easy immature cell source potentially useful for novel approaches for liver regeneration.

Aged↗

PubMed2005

Does 12 weeks of regular standing prevent loss of ankle mobility and bone mineral density in people with recent spinal cord injuries?

The purpose of this study was to determine the effects of a 12-week standing program on ankle mobility and femur bone mineral density in patients with lower limb paralysis following recent spinal cord injury. An assessor-blinded within-subject randomised controlled trial was undertaken. Twenty patients with lower limb paralysis following a recent spinal cord injury were recruited. Subjects stood weight-bearing through one leg on a tilt-table for 30 minutes, three times each week for 12 weeks. By standing on one leg a large dorsiflexion stretch was applied to the ankle and an axial load was applied to the bones of the weight-bearing leg. Ankle mobility and femur bone mineral density of both legs were measured at the beginning and end of the study. Ankle mobility (range of motion) was measured with the application of a 17 Nm dorsiflexion torque. Femur bone mineral density was measured using dual energy X-ray absorptiometry (DEXA). The effect of standing was estimated from the difference between legs in mean change of ankle mobility and femur bone mineral density. The results indicated a mean treatment effect on ankle mobility of 4 degrees (95% CI 2 to 6 degrees) and on femur bone mineral density of 0.005 g/cm(2) (95% CI -0.015 to 0.025 g/cm(2)). Tilt-table standing for 30 minutes, three times per week for 12 weeks has a small effect on ankle mobility, and little or no effect on femur bone mineral density. It is unclear whether clinicians and patients would consider such effects to be clinically worthwhile.

Adult↗

PubMed2000

The role of metalloproteinases and adhesion molecules in interleukin-8-induced stem-cell mobilization.

The chemokine interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. Upon systemic injection, IL-8 induces an immediate neutropenia followed by a rebound granulocytosis. In this report, we discuss the effects of IL-8 on the mobilization of hematopoietic stem cells. Within 20 minutes following a single intraperitoneal injection in mice, IL-8 induces the mobilization of hematopoietic progenitor cells (HPC) with colony-forming, radioprotective, and long-term lymphomyeloid resubpopulating ability. Mobilization can be specifically prevented by pretreatment with antibodies against the beta2 integrin LFA-1 (CD11a). In monkeys, IL-8 Induces the rapid release of the metalloproteinase gelatinase-B concurrent with the mobilization of HPC. The latter effect can be prevented by blocking gelatinase-B activity using specific monoclonal antibodies, suggesting the involvement of gelatinase-B as a mediator of HPC mobilization. These results are consistent with the hypothesis that neutrophils are major regulators of stem-cell mobilization through the release of metalloproteinases (MMPs) that cleave extracellular matrix molecules to which HPC are attached.

Animals↗

PubMed2000

Kinetics of engraftment of CD34(-) and CD34(+) cells from mobilized blood differs from that of CD34(-) and CD34(+) cells from bone marrow.

OBJECTIVE: Mobilized peripheral blood (PB) progenitors are increasingly used in autologous and allogeneic transplantation. However, the short- and long-term engraftment potential of mobilized PB or bone marrow (BM) has not been directly compared. Although several studies showed that BM-derived Lin(-)CD34(-) cells contain hemopoietic progenitors, no studies have addressed whether Lin(-)CD34(-) cells from mobilized PB contain hemopoietic progenitors. Here, we compared the short- and long-term engraftment potential of CD34(+) cells and Lin(-)CD34(-) cells in BM and PB of normal donors who received 5 days of granulocyte colony-stimulating factor (G-CSF). MATERIALS AND METHODS: 35 x 10(3) CD34(+) or Lin(-)CD34(-) cells from G-CSF mobilized BM and PB of normal donors were transplanted in 60-day-old fetal sheep. Animals were evaluated 2 and 6 months after transplantation for human hemopoietic cells. In addition, cells recovered after 2 months from fetal sheep were serially passaged to secondary and tertiary recipients to assess long-term engrafting cells. RESULTS: Mobilized PB CD34(+) cells supported earlier development of human hemopoiesis than BM CD34(+) cells. When serially transferred to secondary and tertiary recipients, earlier exhaustion of human hematopoiesis was seen for PB than BM CD34(+) cells. A similar degree of chimerism was seen for Lin(-)CD34(-) cells from PB or BM in primary recipients. We again observed earlier exhaustion of human hemopoiesis with serial transplantation of PB than BM Lin(-)CD34(-) cells. CONCLUSIONS: Differences exist in the short- and long-term repopulating ability of cells in PB and BM from G-CSF mobilized normal donors, and this is independent of the phenotype. Studies are ongoing to examine if this reflects intrinsic differences in the repopulating potential between progenitors from PB and BM, or a lower frequency of long-term repopulating cells in PB than BM CD34(+) and Lin(-)CD34(-) cells, that may not be apparent if larger numbers of cells are transplanted.

Animals↗

PubMed2002

Mobilization by either cyclophosphamide or granulocyte colony-stimulating factor transforms the bone marrow into a highly proteolytic environment.

OBJECTIVE: Hematopoietic stem and progenitor cells normally reside in the bone marrow but can be mobilized into the peripheral blood following treatment with granulocyte colony-stimulating factor (G-CSF) or myelosuppressive chemotherapy. Although the number of transplants performed with mobilized blood currently exceeds those performed with bone marrow, little is known of the molecular mechanisms responsible for this phenomenon. We sought to determine whether mobilization induced by G-CSF or chemotherapy was triggered by common or distinct mechanisms. METHODS: Balb/c mice were mobilized with either G-CSF alone, cyclophosphamide alone, or the combination of both agents. Spleens, peripheral blood, bone marrow extracellular fluids, and cells were taken at different time points and analyzed for the expression of VCAM-1, the number of peripheral blood progenitor cells, concentration of neutrophil proteases, and number of granulocytes. RESULTS: Administration of either G-CSF or the myelosuppressive agent cyclophosphamide results in a sharp reduction of VCAM-1/CD106 expression in the bone marrow that coincides with the accumulation of granulocytic precursors and release of active neutrophil proteases neutrophil elastase and cathepsin G that directly cleave VCAM-1/CD106 in vitro. These events follow precisely the kinetics of hematopoietic progenitor cell mobilization into the peripheral blood. CONCLUSION: We have identified a commonality of events during mobilization induced by either G-CSF or chemotherapy, which include the accumulation in the bone marrow of active neutrophil proteases that directly cleave VCAM-1 and lead to the sharp reduction of VCAM-1 expression in this tissue.

Animals↗

PubMed2002

Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells.

Mobilization of hematopoietic stem and progenitor cells from the bone marrow into the circulation by repetitive, daily stimulations with G-CSF alone, or in combination with cyclophosphamide, is increasingly used clinically; however, the mechanism is not fully understood. Moreover, following mobilization stem cells also home back to the bone marrow, suggesting that stem cell release/mobilization and homing are sequential events with physiological roles. Previously, a role for cytokines such as G-CSF and SCF, and adhesion molecules such as VLA-4 and P/E selectins, was determined for stem cell mobilization. Recent results using experimental animal models and samples from clinical mobilization protocols demonstrate major involvement of chemokines such as stromal derived factor-1 (SDF-1) and IL-8, as well as proteolytic enzymes such as elastase, cathepsin G, and various MMPs in the mobilization process. These results will be reviewed together with the central roles of SDF-1 and CXCR4 interactions in G-CSF or G-CSF in combination with cyclophosphamide-induced mobilization. Furthermore, the central role of this chemokine in stem cell homing to the bone marrow as well as retention of undifferentiated cells within this tissue will also be discussed.

Animals↗

PubMed1999

Use of mobile low-bandwith telemedical techniques for extreme telemedicine applications.

BACKGROUND: Telemedicine is traditionally associated with the use of very expensive and bulky telecommunications equipment along with substantial bandwidth requirements (128 kilobytes per second [kbps] or greater). Telementoring is an educational technique that involves real-time guidance of a less experienced physician through a procedure in which he or she has limited experience. This technique has been especially dependent on the aforementioned requirements. Traditionally, telemedicine and telementoring have been restricted to technically sophisticated sites. The telemedicine applications through the existing telecommunication infrastructure has not been possible for underdeveloped parts of the world. STUDY DESIGN: Telemedicine and telementoring were applied using low-bandwidth mobile telemedicine applications to support a mobile surgery program in rural Ecuador run by the Cinterandes Foundation and headed by Edgar Rodas, MD. A mobile operating room traveled to a remote region of Ecuador. Using a laptop computer equipped with telemedicine software, a videoconferencing system, and a digital camera, surgical patients were evaluated and operative decisions were made over low-bandwidth telephone lines. Similarly, surgeons in the mobile unit in Ecuador were telementored by an experienced surgeon located thousands of miles away at Yale University School of Medicine. RESULTS: Five preoperative evaluations were conducted from Sucua to Cuenca, Ecuador, with excellent clinical correlation. Additionally, a laparoscopic cholecystectomy was successfully telementored from the department of surgery at Yale University School of Medicine to the mobile surgery unit in Ecuador. The telementored surgery was performed using a telephone line with a baud rate of 12 kbps. CONCLUSIONS: Mobile, low-bandwidth telemedicine applications used in the proper technical and clinical algorithms can be very effective in supporting remote health care delivery efforts. Advantages of such applications include increased cost-effectiveness by limiting travel, expanding services to patients, and increased patient quality assurance.

Ecuador↗

PubMed1997

Peripheral blood stem cell (PBSC) mobilization with chemotherapy followed by sequential IL-3 and G-CSF administration in extensively pretreated patients.

Extensive pretreatment has been identified as a significant risk factor for failure of sufficient PBSC mobilization. From published data and our own experience we defined pretreatment variables which render patients at risk for not collecting at least 2.5 x 10(6) CD34-positive cells per kg bodyweight (BW). These variables were previous unsuccessful PBSC mobilization trial, previous large field radiotherapy, four or more cycles of myelosuppressive chemotherapy regimens, and combinations of extended field radiotherapy plus chemotherapy. Based on these inclusion criteria we treated 19 patients with disease-specific conventional-dose chemotherapy followed by sequential subcutaneous administration of IL-3 (5 microg/kg BW) for 5 consecutive days and G-CSF (10 microg/kg) until PBSC collection or neutrophil recovery. Patients were 10 males and nine females with a median age of 43 years. Diagnoses were non-Hodgkin's lymphoma n = 5, Hodgkin's disease n = 2, multiple myeloma n = 2, CML n = 4, AML n = 4 and testicular cancer n = 2. Twelve patients had prior unsuccessful trial of PBSC mobilization with chemotherapy followed by G-CSF. Except for mobilization chemotherapy-related neutropenic fever, no major toxicities (WHO grade > or = 2) were observed. Growth factors were well tolerated. Collection of at least 2.5 x 10(6) CD34-positive cells per kg BW was possible in 11 out of 19 patients (58%). In five out of 12 patients with a previous unsuccessful trial of PBSC mobilization, the study regimen mobilized sufficient CD34-positive cells. Nine patients went on to high-dose chemotherapy followed by autologous PBSC transplantation. Prompt hematologic recovery was seen in all of them. In conclusion, the sequential administration of IL-3 followed by G-CSF after conventional-dose chemotherapy allows successful PBSC collection in the majority of extensively pretreated patients.

Adult↗

PubMed1999

Changes in endogenous TPO levels during mobilization chemotherapy are predictive of CD34+ megakaryocyte progenitor yield and identify patients at risk of delayed platelet engraftment post-PBPC transplant.

Patients with delayed platelet recovery post-PBPC transplant (PBPCT) are a high-risk group for thrombocytopenic bleeding and platelet transfusion dependence. Total CD34+ cell dosage has been proposed as the most important factor influencing the rate of platelet recovery. To achieve the shortest time to platelet engraftment, a minimum leukapheresis target of 10x10(6) CD34+ cells/kg was established for 30 patients. Of the 29 evaluable patients, 62% had rapid (group I: time to platelets >20x10(9)/l < or =10 days and 50x10(9)/l < or =14 days) platelet recoveries while 38% had delayed (group II: 20x10(9)/l >10 days and 50x10(9)/l >14 days) recoveries. Groups I and II were compared for: (1) pretreatment variables; (2) mobilizing capability of CD34+ cells and subsets including megakaryocyte (Mk) progenitors; (3) infused dose of these cells at transplant; (4) changes in endogenous levels of Mpl ligand (or TPO) during mobilization and myeloablative chemotherapy. Group II patients received significantly more platelet transfusions (6 vs. 2.1, P = 0.002) post-PBPCT, had a higher proportion of patients with a prior history of BM disease (64% vs. 6%, P = 0.001), and showed a reduced ability to mobilize differentiated (CD34+/38+, CD34+/DR+) and Mk progenitors (CD34+/42a+, CD34+/61+). Only the number of Mk progenitors reinfused at transplant was significantly different between the groups (group II vs. group I: CD34+/42a+ = 1.02 vs. 2.56x10(6)/kg, P = 0.013; CD34+/61+ = 1.12 vs. 2.70x10(6)/kg, P = 0.015). The ability to mobilize Mk progenitors correlated with percentage changes in endogenous levels of TPO from baseline to platelet nadir during mobilization chemotherapy (CD34+/42a+: r = 0.684, P = 0.007; CD34+/61+: r = 0.684, P = 0.007), with group II patients experiencing lower percentage changes. An inverse trend but no correlation was observed between serial TPO levels and platelet counts. TPO levels remained elevated in group II patients throughout a prolonged period of thrombocytopenia (median days to 50x10(9)/l = 25 vs. 11 for group I), indicating that delayed engraftment was not due to a deficiency of TPO but to a lack of Mk progenitor target cells. Our results show that the number of reinfused Mk progenitors is a better predictor of platelet engraftment than total CD34+ cell dosage. Small changes in endogenous TPO levels during mobilization predict for low Mk progenitor yields.

Adult↗

PubMed2000

Use of concurrent G-CSF + GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells in children with malignant disease.

There is limited experience in the mobilization of peripheral blood progenitor cells (PBPC) in children and the optimal method for PBPC mobilization is unknown. The present study was conducted to ascertain whether mobilization with G-CSF + GM-CSF (group I) provides some advantage over G-CSF alone (group II) in terms of collected CD34+ cells and hematopoietic recovery following myeloablative conditioning in children with malignancies. An economic analysis was also performed. Each group comprised 21 consecutive patients. The mean number of aphereses was 1.5+/-0.5 in group I and 1.2+/-0.46 in group II (NS). The mean number of CD34+ cells was 3.8 x 106+/-4.03/kg in group I and 4.2+/-5.4 in group II (NS). The mean number of total blood volumes (TBV) processed was 4.4+/-1.5 in group I and 4.3+/-1.5 in group II (NS). The mean duration of the procedure was 276+/-74.1 min in group I and 286.7+/-75.9 min in group II (NS), and the inlet flow was 45.1+/-12 ml/min in group I and 39.5+/-15.1 ml/min in group II (NS). No significant differences in the neutrophil and platelet engraftment probability were observed between the two groups. The mean overall cost of group II was not statistically significant from that of group I (US$ 9521+/-330 vs US$ 10201+/-1028, P = NS). The cost of mobilization was significantly higher in group I than in group II, conditioning regimen costs were similar in both groups and the costs related to the post-transplant period were similar in both groups. We conclude that PBPC mobilization with G-CSF + GM-CSF in children does not enhance hematological recovery in comparison with mobilization using G-CSF alone. However, the combination of G-CSF + GM-CSF does not significantly increase the overall cost of transplantation.

Adolescent↗

PubMed2001

Topotecan-filgrastim combination is an effective regimen for mobilizing peripheral blood stem cells.

We compared the efficacy, toxicity, and cost of topotecan-filgrastim and filgrastim alone for mobilizing peripheral blood stem cells (PBSCs) in 24 consecutive pediatric patients with newly diagnosed medulloblastoma. PBSCs were mobilized with an upfront window of topotecan-filgrastim for 11 high-risk patients (residual tumor > or =1.5 cm2 after resection; metastases limited to neuraxis) and with filgrastim alone for 13 average-risk patients. All patients subsequently underwent craniospinal irradiation and four courses of high-dose chemotherapy with stem cell rescue. Target yields of CD34+ cells (> or =8 x 10(6)/kg) were obtained with only one apheresis procedure for each of the 11 patients treated with topotecan-filgrastim, but with a mean of 2.3 apheresis procedures for only six (46%) of the 13 patients treated with filgrastim alone (P = 0.0059). The median peak and median total yield of CD34+ cells were six-fold higher for the topotecan-filgrastim group (328/microl and 21.5 x 10(6)/kg, respectively) than for the filgrastim group (54/microl and 3.7 x 10(6)/kg, respectively). Mean times to neutrophil and platelet engraftment were similar. Myelosuppression was the only grade 4 toxicity associated with topotecan-filgrastim mobilization and lasted a median of 5 days. Compared with filgrastim mobilization, topotecan-filgrastim mobilization resulted in a mean cost saving of $3966 per patient. Topotecan-filgrastim is an efficacious, minimally toxic, and cost-saving combination for PBSC mobilization.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Mobilization of peripheral blood progenitor cells with vinorelbine and granulocyte colony-stimulating factor in multiple myeloma patients is reliable and cost effective.

Cyclophosphamide with granulocyte colony stimulating factor (G-CSF) is commonly used to mobilize stem cells in multiple myeloma. Timing of collection is variable and incidence and severity of side effects is substantial. To optimize timing of collection, to reduce side effects and to limit costs of the procedure, we evaluated vinorelbine, a drug shown to have activity in multiple myeloma, in combination with G-CSF as mobilizing regimen. A total of 19 consecutive patients with advanced stage multiple myeloma received one dose of vinorelbine 35 mg/m(2) intravenously on day 1 in an outpatient setting and G-CSF 10 microg/kg/day from day 4 divided in two daily doses. Median CD34+ cell blood counts measured on day 8 of mobilization were 142 x 10(6)/l (range 57-467). One 15-l apheresis on day 8 resulted in sufficient stem cells (median 11.1 x 10(6) CD34+ cells/kg, range 6.2-36.0 prior and median 7.5 x 10(6) CD34+ cells/kg, range 4.0-20.2 post-positive CD34+ cell selection) for transplantation. Hematopoietic recovery was swift with ANC >0.5 x 10(9)/l on day 11 median (range 10-15) and platelets >20 x 10(9)/l on day 12 median (range 10-15) after reinfusion of the stem cells on day 0. No episodes of febrile neutropenia were observed during mobilization. In our institutions cost reduction for the procedure was about 1700 euros compared to the mobilization with cyclophosphamide and G-CSF. Vinorelbine and G-CSF allow precise timing and harvesting of sufficient stem cells, and might be an alternative to cyclophosphamide in the mobilization of stem cells for autologous transplantation in multiple myeloma.

Aged↗

PubMed2003

The whys and hows of hematopoietic progenitor and stem cell mobilization.

Intentional mobilization of hematopoietic/stem cells into the circulation has improved the efficiency of their collection. Transplantation of mobilized blood stem cells to patients with marrow aplasia results in a faster pace of hematopoietic recovery than transplantation of marrow-derived stem cells. Autologous and allogeneic hematopoietic stem cell transplantation are increasingly performed with blood-derived cells. Donors of both autologous and allogeneic blood stem cells do not always respond well to therapies designed to produce mobilization. Autologous donors may respond poorly as a result of myelotoxic damage inflicted by prior antitumor therapy, but this explanation is not valid for allogeneic donors. The mechanism(s) involved in the process of mobilization are incompletely understood. Until these mechanisms are elucidated, methods to improve mobilization vigor on a rational basis will not be obvious. In the meanwhile, clinical observations may provide some hints regarding the whys and hows of mobilization and permit incremental improvements in this process.

Animals↗

PubMed2003

G-CSF alone vs cyclophosphamide plus G-CSF in PBPC mobilization of patients with lymphoma: results depend on degree of previous pretreatment.

We performed a randomized study to compare 'G-CSF alone' (administered at dose of 10 mcg/kg/day) and 'cyclophosphamide plus G-CSF' (cyclophosphamide at dose of 4 g/m(2) and G-CSF at dose of 10 microg/kg/day), as PBPC mobilization schedules in 52 patients with NHL or HD. Randomization was stratified according to the amount of previous chemotherapy (< or =2 and >2 lines of previous chemotherapy). Mean CD34+ cell peak in P.B., mean 'Total CD34+ cells' harvested and percentage of patients successfully mobilized, in the group mobilized with 'G-CSF alone' vs the group mobilized with 'cyclophosphamide plus G-CSF', were: 35.3 x 10(6) vs 45.8 x 10(6)/l (P=0.3), 5.4 x 10(6) vs 6.8 x 10(6)/kg (P>0.9) and 50 vs 61% (P=0.4). No differences were observed in the stratum of less pretreated patients. However, in the stratum of patients who had previously received more than two lines of chemotherapy, CD34+cell peak (P=0.05) and percentage of successful mobilization (P=0.01) were higher when 'cyclophosphamide plus G-CSF' was used. Using logistic regression, both age and mobilization with 'G-CSF alone' were significantly associated with a low CD34+ cell peak in P.B. However, in the stratum of less pretreated patients, only age was significantly associated with this risk.

Adult↗

PubMed2004

A single prior course of BCNU-cisplatin chemotherapy has a significant deleterious effect on mobilization kinetics of otherwise untreated patients.

Extensive prior treatment with cytotoxic agents is associated with impaired mobilization of hematopoietic cells. To assess the effect of a single course of standard-dose chemotherapy (CT), we compared the results of filgrastim-induced mobilization among two sequential groups of grade III-IV malignant glioma patients included in a hematopoietic transplantation program. The first group (21 patients) had never been treated with CT until 2 days after surgery, when they received a course of 100 mg/m2 BCNU (i.v.) and 100 mg intracarotid cisplatin for cytoreduction (not for mobilization). At 1 month after this CT, they were mobilized with 12 microg/kg filgrastim. The second group (22 patients) was mobilized with the same dose of filgrastim directly after the surgery, without having ever received any prior CT. The blood level of CD34+ cells was significantly lower in the CT-treated patients, both on the fourth day of filgrastim (15 vs 36 cells x 10(6)/l; P=0.01) and on the fifth (25 vs 58 cells x 10(6)/l; P=0.003), as it was the number of CD34+ cells collected per apheresis (1.3 vs 3.5 x 10(6)/l; P<0.0005). The toxic effect of a single course of BCNU-cisplatin CT led to significant impairment of the filgrastim-induced mobilization response.

Adult↗

PubMed2004

Analysis of remobilization success in patients undergoing autologous stem cell transplants who fail an initial mobilization: risk factors, cytokine use and cost.

Inadequate stem cell mobilization is seen in approximately 25% of patients undergoing autotransplantation for hematologic malignancies. Remobilization strategies include chemotherapy/cytokine combinations or high-dose cytokines alone or in combination. From 1/1997 to 7/2002, we remobilized 86 patients who failed an initial mobilization (median total CD34=0.72 x 10(6)/kg) in sequential cohorts using high-dose G-CSF (32 microg/kg/day) or G-CSF(10 microg/kg/day)+GM-CSF (5 microg/kg/day). No difference in CD34/kg yields were seen (G-CSF alone: 2.2 x 10(6) and G-CSF+GM-CSF 1.6 x 10(6)) in the median 3 aphereses performed (P=0.333). Of the 86, 23 (27%) failed the second mobilization; 14 were remobilized again (yield=1.5 x 10(6) CD34/kg; three aphereses). Of the 86, 93% went to transplant: three progressed, and three had inadequate stem cells. Significant risk factors for a failed remobilization were: number of stem-cell-damaging regimens (P=0.015), time between last chemotherapy and first mobilization (P=0.028), and higher WBC at initiation of first mobilization (P=0.04). High-dose G-CSF (32 microg/kg/day) was more costly @ USD $9,016, vs $5,907 for the G-CSF+GM-CSF combination (P<0.001). Most patients failing an initial mobilization benefit from a cytokine only remobilization. Lower cost G-CSF+GM-CSF is as effective as high-dose G-CSF.

Adult↗

PubMed2002

Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors.

Adult bone marrow (BM) is a rich reservoir for endothelial and hematopoietic stem and progenitor cells that contribute to revascularization of injured and tumor tissue. Physiological stress results in the release of specific chemo-cytokines that promote mobilization of stem cells to the circulation and direct their incorporation into the target tissues. In order to dissect the mechanism and identify the cellular mediators that regulate stem cell recruitment, we have developed an in vivo murine model, in which the plasma levels of chemokines are elevated by introducing adenoviral vectors (Advectors) expressing such chemokines. Among the known stem cell-active chemokines, the angiogenic factor VEGF through interaction with its receptors, VEGFR2 and VEGFR1 expressed on endothelial and hematopoietic stem cells, promotes mobilization and recruitment of these cells into the neo-angiogenic sites, thereby accelerating the revascularization process. Based on these studies, it has become apparent that mobilization of stem cells is a dynamic process and requires sequential release of chemocytokines, expression of adhesion molecules and activation of proteases that facilitate egress of cells from the BM to the circulation. Chemokine-activation of metalloproteinases is essential for the release of bio-active cytokines, thereby enhancing stem cell mobilization potential. Advectors are ideal for delivery of chemocytokines since they allow for long-term robust expression facilitating in vivo proliferation and mobilization of large numbers of an otherwise rare population of stem cells. VEGF-mobilized endothelial and hematopoietic stem cells provide for an enriched source of adult pluripotent cells that can be used for revascularization, tissue regeneration or gene therapy.

Adenoviridae↗