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Results for “Mobility”

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PubMed1996

Influence of initial implant mobility on the integration of titanium implants. An experimental study in rabbits.

In the present study, the influence of initial instability on the healing of titanium implants was studied in 9 lop-eared rabbits. Titanium implants (Brånemark System) were inserted in the tibiae, a location with cortical bone only, in such a way that they were either stable (control), rotation-mobile, or totally mobile. Implants were also inserted in the distal femoral condyles, representing an implantation bed with mainly cancellous bone, so they either showed no initial mobility (control) or were rotation-mobile. After 12 weeks of healing, the implants were retrieved, together with surrounding bone, fixed, dehydrated, and embedded in plastic resin. About 10 micron thick ground sections were prepared for light microscopic morphometry. The mineralized bone to titanium contact, and the amount of bone occupying the threads, were calculated, whereafter the outcome of the different locations were compared. All retrieved implants were clinically stable at the of the experiment. For the tibia sites, a statistically significant less bone to titanium contact, and a less amount of bone in the threads, were found for the totally mobile implants, as compared to the corresponding initially stable controls. Moreover, a statistically significant higher amount of bone was found in the threads of the rotation-mobile implants inserted in the femoral condyle as compared to their initially stable controls. The study indicated that initial rotation-mobility, independent if it occurs in cortical or trabecular bone, does not necessarily lead to an inferior integration of unloaded implants. However, initial total implant mobility within the cortical layer results in a statistically significant less amount of bone around the implants, as compared to stable controls.

Animals↗

PubMed1996

Differential mobilization of fatty acids from adipose tissue.

Are the different fatty acids mobilized into plasma in proportion to their concentrations in adipose tissue triglyceride? To answer this question, we fed weaning rabbits a special diet to label the fat stores with a variety of dietary fatty acids. The release of adipose tissue fatty acids into the plasma was then induced by ACTH-stimulated lipolysis. The compositions of the resulting plasma free fatty acids and of the adipose tissue triglyceride were then compared. Plasma free fatty acids increased from 625 mumol/L at baseline to 2938 mumol/L after ACTH and represented fatty acids released from adipose tissue. The relative mobilization of these fatty acids from adipose tissue was defined as the ratio between their percentage in the plasma free fatty acid fraction to their percentage in adipose tissue triglyceride. For the 24 fatty acids examined, the relative mobilization ranged from 0.11 for 22:1 n-11 to 5.06 for 20:5 n-3, a 46-fold difference. Relative mobilization correlated positively with unsaturation and negatively with chain length. The relative mobilization for essential fatty acids was in the order of 20:5 n-3 > 20:4 n-6 > 18:3 n-3 > 22:6 n-3 > 18:2 n-6. Saturated fatty acids, along with oleic acid, were much less well mobilized than the entire group of polyunsaturated fatty acids. Our data indicate that the mobilization of fatty acids into plasma was not proportional to their content in adipose tissue, but rather was influenced by their molecular structure. Eicosapentaenoic acid 20:5 n-3 (EPA), and arachidonic acid 20:4 n-6, precursors of two different prostaglandins, were the fatty acids with the highest mobilization into the plasma.

Adipose Tissue↗

PubMed1997

In vivo effects of Flt3/Flk2 ligand on mobilization of hematopoietic progenitors in primates and potent synergistic enhancement with granulocyte colony-stimulating factor.

The Flt3 receptor is expressed in primitive hematopoietic cells and its ligand exerts proliferative effects on these cells in vitro in synergy with other cytokines. To expand on the functional properties of Flt3 ligand (FL) in vivo we treated nonhuman primates with FL and tested its ability to mobilize stem/progenitor cells when given alone or in combination with granulocyte colony-stimulating factor (G-CSF) treatment. FL alone (200 microg/kg/day) mobilizes progenitors with slow kinetics and with a peak effect at the end of 2 weeks of treatment. The spectrum of mobilized progenitors includes myeloid, lymphoid, megakaryocytic, and osteoclastogenic but a low proportion of burst-forming unit (BFU)e. Bone marrow (BM) studies before and during the treatment suggested that proliferative effects in BM may have preceded effects on peripheral blood mobilization. To assess the synergy of FL with G-CSF in mobilization of progenitors we used two schemes: one in which G-CSF was used for the last 5 days of a 12-day treatment with FL; the other in which both cytokines were given concurrently for 5 days only (FL, 200 microg/kg; G-CSF, 100 microg/kg). Both schemes yielded much higher progenitor mobilization levels (peak levels of colony-forming cells [CFSs] 41,000 to 95,000/mL blood) than observed with either FL (CFC 4,600 to 7,300/mL) or G-CSF (8,405 +/- 3,024/ mL) used alone at the same doses. Furthermore, there was a progressive and significant expansion of progenitors in vitro during 2 weeks in suspension cultures of mononuclear cells or of CD34+ cells only in the animal with the combined treatment. Likewise, substantial mobilization of osteoclastogenic progenitors was documented only with the combined treatment. Given the functional properties of FL, its synergistic mobilization with G-CSF, and its anticipated good tolerance (because of the absence of an effect on mast cell activation), a clinical use is projected for this cytokine in peripheral blood transplantation settings, as well as in experiments with ex vivo gene transfer.

Animals↗

PubMed1998

Anti-VLA4/VCAM-1-induced mobilization requires cooperative signaling through the kit/mkit ligand pathway.

Although a large body of data on mobilization have yielded valuable clues, the mechanism(s) dictating egress of stem/progenitor cells during baseline hematopoiesis and after their mobilization are poorly understood. We have previously provided functional in vivo evidence that cytoadhesion molecules, specifically the beta1 integrins, are involved in mobilization; however, the mechanism by which this was achieved was unclear. To provide further insights into the anti-very late antigen 4 (VLA4)/anti-vascular cell adhesion molecule 1 (VCAM-1)-induced mobilization, we used these antibodies to treat mutant mice with compromised growth factor receptor function. We found that mobilization by anti-VLA4 does not depend on a functional granulocyte colony-stimulating factor, interleukin-7 (IL-7), or IL-3alpha receptor. By contrast, the functional kit receptor is required, because W/Wv mice responded minimally, whereas Steel-Dickie (Sl/Sld) responded normally. Both Wv and Sl/Sld mice did not respond to anti-VCAM-1 treatment, in contrast to their +/+ littermates and despite normal levels of VCAM-1 expression in bone marrow cells. The defective response to anti-VCAM-1 in W/Wv mice was corrected after their transplantation with +/+ cells. mev/mev mice showed increased numbers of circulating progenitors before treatment and a heightened response after anti-VLA4 or anti-VCAM-1 treatment. Downmodulation of kit expression was detected in normal bone marrow cells after anti-VLA4 treatment. On the strength of the above findings we conclude that (1) anti-VLA4/VCAM-1-induced mobilization likely requires signaling for stimulation of cell migration; (2) this cooperative signaling involves the kit/kit ligand pathway, and provides a novel example of integrin/cytokine crosstalk; and (3) migration mediated through the kit/kit ligand pathway may be a common contributor to different mobilization stimuli. Dissection of the exact molecular pathways that lead to mobilization remains a future challenge.

Animals↗

PubMed2000

Peripheral blood progenitor cell mobilization in three groups of subjects: a comparison of leukapheresis yield and timing.

In this review, we analyse the peripheral blood progenitor cell mobilization yield of three categories of subjects including group 1, healthy allogeneic donors given growth factors; group 2, patients with haematological malignancies mobilized with chemotherapy followed by growth factors; and group 3, patients with solid tumours mobilized with growth factors alone. A wide variation amongst subjects of the same category was observed. Group 1 and group 2 patients mobilized to a similar degree with a mean CD34(+) yield/kg of 3.44 x 10(6) and 3.39 x 10(6) respectively, for a standardized 2. 5 times blood volumes processed. This is superior to group 3 patients mobilized with growth factors alone who yielded only 0.99 x 10(6)/kg. A good correlation between peripheral blood CD34(+) count and leukapheresis yield was observed for all three groups. For healthy donors, prescheduled leukapheresis on day 5 after growth factors commencement predicts good yield, obviating the need for CD34 monitoring. On the contrary, most cancer patients mobilized with growth factors alone as in group 3 have inadequate single collection. They invariably require cumulative yield of several collections for adequate dose and hence predicting timing with peripheral blood CD34(+) count is not useful. In group 2 patients mobilized with chemotherapy followed by growth factors, we find that a peripheral blood CD34(+) count of 11/microL predicts collection of more than 1 x 10(6) CD34(+) cell/kg/2.5 blood volumes, thus helping to maximize yield and resources. J. Clin. Apheresis, 15:217-223, 2000.

Adult↗

PubMed1994

Mobile cardiac catheterization registry: report of the first 1,001 patients.

The purpose of this study was to evaluate prospectively the efficacy and safety of mobile cardiac catheterization. Mobile cardiac catheterization was introduced into clinical practice in 1989, but there has been no systematic study of its performance and safety. A registry was established in 1989 to monitor outcomes with mobile cardiac catheterization and is reported here. Patients were screened for eligibility for mobile cardiac catheterization using the joint AHA/ACC criteria for outpatient angiography. Eligible patients underwent mobile catheterization at eight hospitals within 120 miles of the base tertiary center. Helicopter evacuation services were available at each mobile site. The indications, findings, dispositions, and complications of mobile cardiac catheterization were recorded by means of a checklist, telephone follow-up and chart review. A total of 1,001 consecutive patients were entered into the registry in the first 20 months of operation, including 436 females and 565 males aged 22 to 84 years. Angina (Canadian Classes II-IV) was the most frequent primary indication for catheterization (46.4%), followed by atypical chest pain (36.9%), or a positive exercise stress test (25.6%). Infrequent indications for catheterization included a history of myocardial infarction (5.6%), congestive heart failure (7.1%), arrhythmias (4.1%), and valvular heart disease (0.7%). Catheterization was accomplished in 99.9% of patients. Angiographically normal studies were observed in 22.8%, and mild (< or = 50%) coronary artery disease in 13.6% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2005

CpG-oligodeoxynucleotides induce mobilization of hematopoietic progenitor cells into peripheral blood in association with mouse KC (IL-8) production.

The immune system of vertebrates detects bacterial DNA as a "danger signal" based on the presence of unmethylated CpG motifs. We examined whether oligodeoxynucleotides (ODNs) with CpG motifs (CpG-ODNs) also induce mobilization of hematopoietic progenitor cells (HPCs). Mice challenged with CpG-ODNs showed an increase in peripheral blood colony-forming units (CFU) with a peak at day 4 after treatment, associated with an increase, starting 30 min after CpG treatment, in serum levels of mouse keratinocyte-derived chemokine (mKC), a functional homolog of human interleukin (IL) 8; production of granulocyte-colony-stimulating factor (CSF) was also detected. Mobilization and mKC induction were sequence-specific and dose-dependent occurring even with low doses of CpG-ODNs. Interestingly, intestinal cells were involved in mKC production. HPC mobilization by CpG-ODNs was dependent on peripheral blood mononuclear cells since mobilization was reduced in neutrophil-depleted mice. Moreover, CpG-ODN treatment significantly increased G-CSF mobilizing capacity. Finally, pretreatment with an anti-mKC neutralizing antibody significantly reduced CpG-induced mobilization, further supporting a role for mKC. Thus, bacterial DNA is a "danger signal" not only for immune cells but also for hematopoietic cells, communicating the need for increased hematopoiesis during infections and for the renewal of the immune system. The HPC mobilization activity of CpG-ODNs will need to be considered in the design of treatment regimens for cancer clinical trials using CpG-ODNs in association with chemotherapy.

Animals↗

PubMed2002

Mobilization of allogeneic peripheral blood progenitor cells.

It is possible to reliably obtain sufficient PBSC from most normal donors to perform allogeneic transplantation. The mobilization regimen, usually administration of a single daily dose of G-CSF at 7.5 to 10 micrograms/kg subcutaneously for 4 to 6 days, is tolerable with acceptable side effects. However, there is wide variability among individuals with respect to the extent of mobilization achieved by the regimen and the optimal timing of apheresis. Studies suggest that the likelihood of obtaining an adequate harvest of CD34+ cells, as defined locally may be enhanced by employing higher doses or different schedules of G-CSF, monitoring the mobilization and/or collection of PBPC, and using apheresis procedures processing 2 or more times blood volume. However, an optimal regimen for mobilization and harvesting for all donors has not yet been identified and a small percentage of donors may not mobilize adequately with G-CSF. Alternative regimens employing combinations of G-CSF and GM-CSF are available that may prove useful in such cases and novel cytokines that are even more effective than G-CSF in mobilizing stem cells are eagerly awaited. Based on currently available experience with normal donors, the short-term safety of G-CSF appears to be acceptable, however there exist several scenarios in which marrow harvesting may be preferable to G-CSF mobilization and apheresis collection of PBPC.

Adult↗

PubMed2004

Infection control practices for SARS in Lao People's Democratic Republic, Taiwan, and Thailand: experience from mobile SARS containment teams, 2003.

BACKGROUND: Despite available recommendations on infection control for severe acute respiratory syndrome (SARS), information is limited on actual practices in Asian hospitals during the epidemic. We describe practices observed by mobile SARS containment teams (mobile teams) during outbreak investigations. METHODS: We retrospectively summarized infection control practices observed in hospitals visited by mobile teams in the Lao People's Democratic Republic (PDR), Taiwan, and Thailand, during March and April 2003. RESULTS: Mobile teams investigated 22 reports of SARS in 20 hospitals (1, 5, and 14 hospitals in Lao PDR, Taiwan, and Thailand, respectively). Facilities ranged from urban hospitals with negative-pressure isolation rooms and high-efficiency particulate air filtration to rural hospitals with patient rooms open to outside air circulation and intermittent running water. At the time of mobile team visits, 5 (25%) hospitals implemented infection control practices consistent with World Health Organization recommendations on visitor policies, private negative-pressure rooms, and personal protective equipment. CONCLUSIONS: Early in the SARS epidemic, mobile teams found wide variations in infection control practices and resources among Asian hospitals evaluating patients for SARS, indicating the importance of ongoing assessment during SARS preparedness. Mobile teams are one mechanism to assess practices and promote implementation of recommended infection control measures.

Communicable Disease Control↗

PubMed2004

Growth factors mobilize CXCR4 low/negative primitive hematopoietic stem/progenitor cells from the bone marrow of nonhuman primates.

Abstract The chemokine receptor CXCR4 is expressed by CD34 + hematopoietic stem/progenitor cells (HSC/HPC). Several investigators have suggested that expression of CXCR4 may be an important characteristic of HSC/HPC. We studied the dynamic expression of CXCR4 during growth factor-induced mobilization of HSC in a clinically relevant nonhuman primate model, Papio anubis (baboons). We evaluated whether CXCR4 expression in HSC/HPC varies during steady-state hematopoiesis as well as during growth factor-induced mobilization. Peripheral blood stem cells from 5 baboons were mobilized with growth factors. During mobilization, there was a consistent stepwise increase in the proportion of peripheral blood CD34 + cells that were CXCR4 -. The highest number of CD34 + CXCR4 - cells appeared in the peripheral blood at the same time as the maximum number of assayable colony-forming cells. The cloning efficiency of the CD34 + CXCR4 - population was 3-fold greater than that of CD34 + CXCR4 + cells, and the frequency of cobblestone area-forming cells was 6 times higher in the CD34 + CXCR4 - population in comparison to CD34 + CXCR4 + cells. Furthermore, the most quiescent CD34 + cells isolated on the basis of low Hoechst 33342 (Ho) and rhodamine 123 (Rho) staining (Ho Low /Rho Low ) were highly enriched in the CXCR4 Low/- cell population. Ex vivo incubation of mobilized peripheral blood CD34 + cells with growth factors for 40 hours resulted in increasing numbers of cells expressing CXCR4. Peripheral blood stem cell grafts containing CD34 + cells that consisted of predominantly CXCR4 - cells were able to rapidly engraft lethally irradiated baboons. Because the overwhelming number of CD34 + cells within the mobilized peripheral blood grafts were CXCR4 - and were capable of rescuing lethally irradiated baboons, it seems unlikely that the expression of CXCR4 in vitro is an absolute requirement for HSC homing and engraftment. In summary, our data suggest the dynamic nature of CXCR4 expression on CD34 + cells during growth factor-induced HSC/HPC mobilization. In addition, our data indicate that the lack of CXCR4 expression is possibly a characteristic of relatively more primitive HSC/HPC characterized by a higher proliferative capacity.

Animals↗

PubMed2006

Allogeneic stem cell transplantation with peripheral blood stem cells mobilized by pegylated G-CSF.

Mobilization of stem cells with pegylated granulocyte colony-stimulating factor (peg-G-CSF) modulates donor T- and natural killer T-cell (NKT-cell) functions, thus separating graft-versus-host from graft-versus-leukemia disease in animal models. We report a phase I/II study that analyzed the feasibility of mobilizing stem cells from normal donors with peg-G-CSF and the ability of these cells to restore hematopoiesis in allogeneic transplant recipients after myeloablative conditioning. Administration of 6 mg of peg-G-CSF resulted in suboptimal stem cell mobilization, with a peak peripheral blood CD34+ count of 29+/-5/microL. Apheresis 4 days after peg-G-CSF yielded 2.7+/-.4x10(6) CD34+ cells/kg recipient weight, and all donors required a second collection on day 5 to yield a total of 4.2+/-.5x10(6) CD34+ cells/kg recipient weight. After escalation of the dose to 12 mg, the peak CD34+ count was 99+/-11/microL and 12 of 13 donors collected sufficient stem cells for transplantation in a single apheresis (8.9+/-1.4x10(6) CD34+ cells/kg recipient weight). Late transient increases in serum hepatic transaminases were noted, but other side effects (predominantly bone pain) were otherwise similar to those seen in donors mobilized with standard G-CSF. Median neutrophil and platelet engraftments occurred on days 18 and 14, respectively, after transplantation and were identical to those seen with in recipients of grafts mobilized with standard G-CSF. With a median follow-up of 357 days, the incidence of grade II-IV acute graft-versus-host disease was 50% and there have been no relapses to date. Mobilization of stem cells with peg-G-CSF in normal donors is feasible and 12 mg results in mobilization characteristics similar to those of standard G-CSF.

Adult↗

PubMed2004

Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells into peripheral blood circulation.

OBJECTIVE: The aim of this study was to investigate the stimulating effect of low-dose radiation (LDR) on bone marrow hematopoietic progenitor cell (HPC) proliferation and peripheral blood mobilization. METHODS: Mice were exposed to 25- to 100-mGy x-rays. Bone marrow and peripheral blood HPCs (BFU-E, CFU-GM, and c-kit+ cells) were measured, and GM-CSF, G-CSF, and IL-3 protein and mRNA expression were detected using ELISA, slot blot hybridization, and Northern blot methods. To functionally evaluate LDR-stimulated and -mobilized HPCs, repopulation of peripheral blood cells in lethally irradiated recipients after transplantation of LDR-treated donor HPCs was examined by WBC counts, animal survival, and colony-forming units in the recipient spleens (CFUs-S). RESULTS: 75-mGy x-rays induced a maximal stimulation for bone marrow HPC proliferation (CFU-GM and BFU-E formation) 48 hours postirradiation, along with a significant increase in HPC mobilization into peripheral blood 48 to 72 hours postradiation, as shown by increases in CFU-GM formation and proportion of c-kit+ cells in the peripheral mononuclear cells. 75-mGy x-rays also maximally induced increases in G-CSF and GM-CSF mRNA expression in splenocytes and levels of serum GM-CSF. To define the critical role of these hematopoietic-stimulating factors in HPC peripheral mobilization, direct administration of G-CSF at a dose of 300 microg/kg/day or 150 microg/kg/day was applied and found to significantly stimulate GM-CFU formation and increase c-kit+ cells in the peripheral mononuclear cells. More importantly, 75-mGy x-rays plus 150 microg/kg/day G-CSF (LDR/150-G-CSF) produced a similar effect to that of 300 microg/kg/day G-CSF alone. Furthermore, the capability of LDR-mobilized donor HPCs to repopulate blood cells was confirmed in lethally irradiated recipient mice by counting peripheral WBC and CFUs-S. CONCLUSION: These results suggest that LDR induces hematopoietic hormesis, as demonstrated by HPC proliferation and peripheral mobilization, providing a potential approach to clinical application for HPC peripheral mobilization.

Animals↗

PubMed2005

Modeling the electrophoretic mobility of beta-blockers in capillary electrophoresis using artificial neural networks.

Artificial neural networks were used for modeling the mobility of five beta-blockers (i.e., labetalol atenolol, practolol, timolol and propranolol) in running buffer with ternary solvent background electrolyte systems containing 80 mM acetate buffer dissolved in water, methanol, ethanol and their ternary mixtures. The volume fractions of two solvents (f(2), f(3)) and cologarithm of electrophoretic mobilities in pure solvents (i.e., -Lnmu(1), -Lnmu(2) and -Lnmu(3)) were used as inputs and cologarithm of the mobility in mixed solvents was the output of the networks. The number of neurons in hidden layer, learning rate, momentum and the number of epochs were optimized, in which two neurons in hidden layer, 0.2, 0.9 and 20000 were found the optimized values for learning rate, momentum and number of epochs, respectively. Mean percentage deviations (MPD) between calculated and experimental mobilities were computed as an accuracy criterion. To assess the correlative ability of the model, all data points in each set were used as training set and the mobilities were back-calculated by the trained networks, in which the overall MPD (OMPD)+/- standard deviation (SD) for correlative study was 3.1+/- 2.3. To evaluate the prediction capability of the proposed ANN model, the network was trained using 15 data points for each analyte and the remaining data points were predicted. The obtained OMPD (+/-SD) for this analysis was 3.6+/-3.0. To further investigate on the applicability of ANN, a generalized network was trained with 10 data points from each beta-blocker and then the network was employed to predict the mobilities of the analytes in ternary solvent electrolyte systems. The MPDs for predicted mobilities were 3.6%, 3.6%, 3.9%, 3.7% and 2.9% respectively for labetalol, atenolol, practolol, timolol and propranolol.

Adrenergic beta-Antagonists↗

PubMed2000

Mechanisms of granulocyte colony-stimulating factor-induced hematopoietic progenitor-cell mobilization.

Hematopoietic progenitor cells (HPC) can be mobilized from the bone marrow into the peripheral circulation in response to diverse stimuli, including hematopoietic growth factors, cytotoxic agents, and certain chemokines. Despite significant differences in their biologic activities, these stimuli result in the mobilization of HPC with a similar phenotype, suggesting that a common mechanism for mobilization may exist. To explore the mechanisms of granulocyte colony-stimulating factor (G-CSF)-induced mobilization, we examined HPC mobilization in mice that are genetically deficient for the G-CSF receptor (G-CSFR). Their response was determined to each of three major types of mobilizing stimuli: cytotoxic agents (cyclophosphamide), chemokines (Interleukin-8[IL-8]), and hematopoietic growth factors (G-CSF, fit-3 ligand, and IL-12). These studies demonstrate that the G-CSFR is required for mobilization in response to cyclophosphamide and IL-8, but not fit-3 ligand or IL-12, and suggest that the G-CSFR may play an important and previously unexpected role in HPC migration.

Animals↗

PubMed1998

Stimulated astrocytes release high-mobility group 1 protein, an inducer of LAN-5 neuroblastoma cell differentiation.

Stimulated astrocytes specifically release large amounts of high-mobility group 1 protein into the extracellular medium. The identity of the released protein has been established on the basis of its biological activity on murine erythroleukaemia cells and by its immunoreactivity against a specific monoclonal antibody. High-mobility group 1 protein also plays an essential role in differentiation of LAN-5 neuroblastoma cells which, following stimulation with retinoic acid, express high-mobility group 1 protein on to the external surface of the plasma membrane. In retinoic acid-induced LAN-5 cells, high-mobility group 1 protein is not secreted but is accumulated in a membrane-bound form, particularly at the level of neurite outgrowths. These cells can also be induced to differentiate by high-mobility group 1 protein coated on the surface of the cell culture vessels. The specific function of the protein in this process is indicated by inhibition of cell differentiation by an anti-high-mobility group 1 protein antibody. The data are consistent with a role of high-mobility group 1 protein in promoting cell-cell interactions and in the development of nerve tissues.

Animals↗

PubMed1999

Matched-pair analysis of hematopoietic progenitor cell mobilization using G-CSF vs. cyclophosphamide, etoposide, and G-CSF: enhanced CD34+ cell collections are not necessarily cost-effective.

Using matched-pair analysis, we compared two popular methods of stem cell mobilization in 24 advanced-stage breast cancer patients who underwent two consecutive mobilizing procedures as part of a tandem transplant protocol. For the first cycle, 10 microg/kg/day granulocyte colony-stimulating factor (G-CSF) was given and apheresis commenced on day 4 and continued for < or =5 days (median 3 days). One week after the first cycle of apheresis, 4000 mg/m2 cyclophosphamide, 400 mg/m2 etoposide, and 10 microg/kg G-CSF were administered for < or =16 days (cycle 2). Apheresis was initiated when the white blood cell (WBC) count exceeded 5000 cells/microL and continued for < or =5 days (median 3 days). Mean values of peripheral blood WBC (31,700+/-3200 vs. 30,700+/-3300/microL) were not significantly different between cycles 1 and 2. Mean number of mononuclear cells (MNC) collected per day was slightly greater with G-CSF mobilization than with the combination of chemotherapy and G-CSF (2.5+/-0.21x10(8) vs. 1.8+/-0.19x10(8) cells/kg). Mean daily CD34+ cell yield, however, was nearly six times higher (12.9+/-4.4 vs. 2.2+/-0.5x10(6)/kg; p = 0.01) with chemotherapy plus G-CSF. With G-CSF alone, 13% of aphereses reached the target dose of 5x10(6) CD34+ cells/kg in one collection vs. 57% with chemotherapy plus G-CSF. Transfusions of red blood cells or platelets were necessary in 18 of 24 patients in cycle 2. Three patients were hospitalized with fever for a median of 3 days after cycle 2. No patients received transfusions or required hospitalization during mobilization with G-CSF alone. Resource utilization (cost of drugs, aphereses, cryopreservation, transfusions, hospitalization) was calculated comparing the median number of collections to obtain a target CD34+ cell dose of 5x10(6) cells/kg: four using G-CSF vs. one using the combination in this data set. Resources for G-CSF mobilization cost $7326 vs. $8693 for the combination, even though more apheresis procedures were performed using G-CSF mobilization. The cost of chemotherapy administration, more doses of G-CSF, transfusions, and hospitalizations caused cyclophosphamide, etoposide, and G-CSF to be more expensive than G-CSF alone. A less toxic and less expensive treatment than cyclophosphamide, etoposide, and G-CSF is needed to be more cost-effective than G-CSF alone for peripheral blood progenitor cell mobilization.

Adult↗

PubMed1997

Efficient peripheral blood stem cell mobilization with low-dose G-CSF (50 microg/m2) after salvage chemotherapy for lymphoma.

We compared the use of low-dose G-CSF (50 microg/m2/day), following salvage chemotherapy, for mobilization of PBSC with the results obtained in a comparable historical control group who received a standard dose of G-CSF (5 microg/kg/day, approximately 200 microg/m2/day). Thirty adult patients with relapsed or refractory lymphoma were treated with ifosfamide, VP-16, intermediate-dose Ara-C, methylprednisolone (IAPVP-16) and G-CSF 5 microg/kg/day (group A, n = 15) or 50 microg/m2/day (group B, n = 15) from day 6 until the end of leukaphereses. The duration of neutropenia and thrombocytopenia were equal in both groups. A median of two (1-3) leukaphereses were performed in both groups to harvest >3.5 x 10(6)/kg CD34+ cells. The numbers of circulating CD34+ cells on the first day of leukocyte recovery were similar in both groups in those patients mobilized after a first cycle of IAPVP-16. The numbers of circulating CD34+ cells were similar in patients mobilized after a first and after a second IAPVP-16 in group A. In the low-dose group (group B), however, the numbers of circulating CD34+ cells were significantly lower in those mobilized after a second than after a first course. Additionally, the product of the first leukapheresis contained significantly fewer CD34+ cells in those mobilized after a second course only in group B, with no differences in group A. Nevertheless, the final products harvested did not differ in the content of MNC, CFU-GM and CD34+ cells, suggesting that these differences are not clinically important. These results indicate that the use of low-dose G-CSF (50 microg/m2/day) is as effective as 5 microg/kg/day in accelerating neutrophil recovery and mobilizing CD34+ cells after a first cycle of IAPVP-16 salvage chemotherapy, resulting in a substantial decrease in costs, while more heavily pretreated patients may require higher doses of G-CSF for an equivalent mobilization.

Adolescent↗

PubMed1999

Comparison of monocyte-dependent T cell inhibitory activity in GM-CSF vs G-CSF mobilized PSC products.

This study compares the immune properties of peripheral blood stem cell (PSC) products mobilized with different hematopoietic growth factors (HGFs) as well as apheresis products and peripheral blood leukocytes (PBL) from normal individuals. We found that monocytes in mobilized PSC products appear to inhibit T cell function independent of whether granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for mobilization. In addition, the GF used to mobilize the stem cell product may be less important to the CD4:CD8 ratio than the extent of prior chemotherapy, as we found an inverse correlation between chemotherapy and the CD4:CD8 ratio. In other observations, all apheresis products, whether mobilized or unmobilized, contained significantly more monocytes compared to normal PBL. The mononuclear cells (MNC) from G-CSF or GM-CSF mobilized PSC products had a similar T cell phytohemagglutinin (PHA) mitogenic response that was significantly lower (P = 0.001 and P = 0.005, respectively) than non-mobilized apheresis products. We also examined the T cell inhibitor (TI) activity of the MNC from the PSC products for allogeneic lymphocyte proliferation and found that PSC products significantly reduced the proliferation of allogeneic PBL to PHA. A significant correlation (P = 0.001, r = 0.517) between the frequency of monocytes and TI activity also was observed.

Adult↗