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PubMed2003

Infectious complications in patients receiving mobilization chemotherapy for autologous peripheral blood stem cell collection.

The purpose of this retrospective study was to evaluate infectious complications in patients receiving mobilization chemotherapy for stem cell collection prior to autologous peripheral blood stem cell transplantation. An additional goal was to evaluate risk factors associated with the development of infectious complications. At the Medical College of Georgia BMT center, 54 patients were administered mobilization chemotherapy for the purpose of collecting stem cells between June, 1997, and May, 2002. All patients received Filgrastim in addition to chemotherapy, and 50 of 54 patients received prophylactic acyclovir, fluconazole, and ciprofloxacin until neutrophil recovery. The median duration to neutrophil recovery was 11 days. Fourteen of 54 (26%) patients developed fever/infections during the mobilization phase. One patient developed both a catheter-related infection and Clostridium difficile colitis, increasing the total number of infectious episodes to 15. Twelve patients had a documented site of infection whereas 2 patients had neutropenic fever with no identifiable source. Eight of the 15 (55%) infections were Gram-positive catheter infections. All the patients were treated successfully with antibiotics. No systemic fungal infections were identified and none of the patients died from complications related to mobilization chemotherapy. Logistic regression was applied for univariate and multivariate analysis and showed that age, sex, diagnosis, neutrophil recovery, disease status, use of salvage chemotherapy, and mobilization regimen used did not affect the infection rate. In our series of 54 patients, 14 patients developed fever/infections during mobilization. Although there is a substantial risk of infectious complications among patients who receive mobilization chemotherapy, it is not clear that prophylactic antibiotics decrease infectious complications. Because the vast majority of infections are Gram-positive catheter infections, it appears reasonable to employ Gram-positive prophylaxis. Controlled studies should be conducted to define the optimum mobilization regimens as well as the optimum combination of prophylactic antibiotics.

Adult↗

PubMed2005

Murine side population cells contain cobblestone area-forming cell activity in mobilized blood.

Primitive hematopoietic stem cells (HSCs) can be purified from murine bone marrow by sorting Hoechst 33342-effluxing side population (SP) cells. The aim of this study was to establish whether SP cells from peripheral blood contain primitive HSCs and whether this is altered in mice following mobilization. SP cells were analyzed and isolated from bone marrow and blood of mice after mobilization; the HSC content of isolated SP cells was determined through surrogate cobblestone area-forming cell (CAFC) assays. SP cells in normal blood were not found in the high Hoechst dye effluxing portion of the SP tail, did not express the stem cell markers c-Kit and CD34, and did not have measurable CAFC activity. In contrast, SP cells in mobilized blood expressed both stem cell markers, contained cells in the high dye efflux portion of the SP tail, and displayed significant day- 28 to day-35 CAFC activity with 165- to 334-fold enrichment. In comparison to mobilized blood SP cells, normal marrow SP cells contained a higher proportion of cells expressing c-Kit and CD34 and had a greater percentage of cells in the high Hoechst dye-effluxing portion of the SP tail. Analysis of SP cells in the bone marrow after mobilization revealed a decrease in the frequency of SP cells, in expression of c-Kit and Sca+ CD34(+)/CD34(-), and in day-7 to day-35 CAFC activity, consistent with mobilization into blood. We conclude that murine SP cells mobilized into blood contain primitive hematopoietic stem cell activity (day-28 to day-35 CAFC activity). This model offers a means to study the mechanisms of mobilization of primitive stem cells directly in a murine model.

Animals↗

PubMed2006

No polarization of type 1 or type 2 precursor dendritic cells in peripheral blood stem cell collections of non-hodgkin's lymphoma patients mobilized with cyclophosphamide plus G-CSF, GM-CSF, or GM-CSF followed by G-CSF.

Dendritic cells (DCs) are the most efficient antigen-presenting cells and play a role in immune reconstitution after autologous transplantation. Recent reports suggest that mobilization with granulocyte colony-stimulating factor (G-CSF) containing regimens polarizes DCs into pDC2, which could potentially result with increased Th2 response and decreased graft-versus-host disease (GVHD) in allogeneic transplantation and with decreased cytotoxic Th1 response and graft versus tumor effect, which in autologous transplantation could translate into increased relapse rate. Previously, we have shown that non-Hodgkin's lymphoma (NHL) patients receiving cyclophosphamide (CTX) plus granulocyte- macrophage (GM)-CSF, G-CSF or GM-CSF followed by G-CSF for stem cell collection, mobilize up to five-fold more mature CD80(+) DCs compared to CTX plus G-CSF mobilized patients. Here, we analyzed samples from the same study for the number of pDC1 and pDC2 subsets in blood and apheresis products obtained from these patients. Samples from 29 patients were collected. Patients mobilized with CTX plus G-CSF collected a mean of 1.2 +/- 0.4 x 10(6) pDC1/kg per day and 2.2 +/- 1 x 10(6) pDC2/kg per day, whereas patients mobilized with CTX plus GM-CSF collected a mean of 1.1 +/- 0.5 x 10(6) pDC1 and 1.5 +/- 0.9 x 10(6) pDC2/kg per day. Patients mobilized with CTX plus GM-CSF followed by G-CSF collected 2.5 +/- 1.1 x 10(6) pDC1 and 2 +/- 0.5 x 106 pDC2/kg per day, with significantly higher levels of pDC1 +/- pDC2 cells. No significant difference was observed in pDC1/pDC2 ratio between the three mobilization arms. Patients mobilized with the GM-CSFcontaining regimen had a higher probability for survival compared to patients receiving G-CSF alone (median of 55 months vs. 15 months; p = 0.02). These results support the hypothesis that higher levels of DCs in the graft might be associated with prolonged survival of autotransplanted NHL patients. Further similar studies are merited in a larger population of NHL patients.

Adult↗

PubMed1989

Regulation of triglyceride mobilization in isolated hepatocytes by dibutyryl cyclic AMP and epinephrine.

Regulation of the mobilization of endogenous fatty acids from lipid droplet triglyceride was investigated in isolated hepatocytes from normal-fed rats. Mobilized fatty acid was entirely accounted for in oxidation products (CO2 plus acid-soluble products). Dibutyryl cyclic AMP (DBcAMP) stimulated the mobilization of endogenous fatty acids by over 50% although no change in free fatty acid (FFA) levels was observed. In the presence of tetradecyglycidic acid (TDGA), a specific inhibitor of mitochondrial fatty acid oxidation, DBcAMP was unable to promote endogenous fatty acid oxidation; instead, the nucleotide increased the FFA level. This effect was blocked by the lysosomal inhibitor, chloroquine, supporting the concept that a lysosomal lipase is involved in the degradation of endogenous triglyceride. These findings suggest that cyclic AMP stimulates lysosomal lipolysis by a mechanism that is independent of changes in fatty acid oxidation. Epinephrine alone slightly suppressed triglyceride mobilization. Epinephrine plus doxazosin slightly increased lipid mobilization. Epinephrine plus propranolol suppressed endogenous fatty acid oxidation to a level significantly below that induced by epinephrine plus doxazosin. These results suggest that alpha 1-adrenoceptor activation suppresses hepatic triglyceride mobilization. The weak stimulatory effects of beta-adrenoceptor activation on hepatocyte triglyceride mobilization compared with the potent stimulation by DBcAMP is probably attributable to the relatively low level of beta-adrenoceptors in hepatocytes from the mature male rats used in these studies. Further characterization of a possible mutually antagonistic interaction between alpha 1- and beta 2-adrenoceptors in the regulation of hepatic triglyceride mobilization might be better accomplished in a species with hepatocytes that have a higher proportion of beta-adrenoceptors, e.g., guinea pig, rabbit, and dog.

Adrenergic alpha-Antagonists↗

PubMed2005

Effect of stem cell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor on morphology of haematopoietic organs in mice.

Both granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (CY) are employed in the clinic as mobilizing agents to stimulate the egress of haematopoietic stem/progenitor cells (HSPC) from bone marrow (BM) into peripheral blood (PB). However, although both compounds are effective, the simultaneous administration of G-CSF + CY allows for optimal mobilization. The aim of this study was to compare morphological changes in major haematopoietic organs in mice mobilized by G-CSF + CY. We employed the standard G-CSF + CY mobilization protocol, in which mice were injected at day 0 with a single dose of CY followed by daily injection of G-CSF for 6 consecutive days. We noticed that the cytoreductive effect of CY on BM and spleen tissue was compensated at day 2 by the pro-proliferative effect of G-CSF. Furthermore, as evidenced by histological examination of BM sections at day 4, egress of haematopoietic cells from BM was accelerated by 2 days as compared to mobilization by G-CSF or CY alone; also, by day 6 there was accumulation of early haematopoietic (Thy-l(low) c-kit+) cells in the spleens and livers of mobilized animals. This implies that HSPC that are mobilized from BM and circulate in PB may 'home' to peripheral organs. We envision that such an accumulation of these cells in the spleen (which is a major haematopoietic organ in mouse) allows them to participate in haematopoietic reconstitution. Their homing to other sites (for example the liver) is evidence that BM-derived stem cells are playing a pivotal role in organ/tissue regeneration. The potential involvement of major chemoattractants for stem cells, like stromal-derived factor-1 which is induced by CY in various regenerating organs such as the liver, requires further study. We conclude that inclusion of CY into mobilization protocols on the one hand efficiently increases the egress of HSPC from the BM, but on the other hand may lead to the relocation of BM stem cell pools to peripheral tissues.

Animals↗

PubMed2006

Efficacy of single-dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma.

BACKGROUND: A single injection of pegfilgrastim has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, whereas the experiences with pegfilgrastim in mobilization of peripheral blood progenitor cells (PBPCs) are limited. STUDY DESIGN AND METHODS: Forty unselected patients with lymphoma or multiple myeloma were treated with different chemotherapy regimens followed by 6 mg of pegfilgrastim for mobilization of autologous PBPCs. Patients with an inadequate mobilization (blood CD34+ cells <or= 10/microL after nadir) were given additional daily doses of 10 microg per kg unconjugated filgrastim. RESULTS: A median blood CD34+ peak concentration of 81 per microL (range, 10-565/microL) was found in 30 patients, who had only received pegfilgrastim, compared to 13 per microL (median, range 4-71/microL; p < 0.001) in 10 poor mobilizing patients with additional filgrastim. The median yield of CD34+ cells was 9.8 x 10(6) per kg (range, 1.5-88.1) after pegfilgrastim only versus 2.5 x 10(6) (range, 1.7-7.0) in poor mobilizers. Patients who needed additional cytokine administration were those with a more extensive previous antineoplastic treatment and mobilizing regimens containing PBPC toxic agents. CONCLUSION: The results confirm the efficacy and feasibility of PBPC mobilization with chemotherapy and single-dose pegfilgrastim in patients with lymphoproliferative malignacies. In less heavily pretreated patients, 6 mg of pegfilgrastim after chemotherapy induced an adequate mobilization, whereas dose and schedule in patients after numerous cytotoxic regimens need further investigation.

Adult↗

PubMed1981

Assessment of tooth mobility using small loads. IV. The effect of periodontal treatment including gingivectomy and flap procedures.

Tooth mobility at loads below 100 p, gingival fluid amounts and bone score heights were studied in five subjects. In all 28 maxillary anterior teeth were investigated during a period of 68 weeks. In order to enlarge upon a previous investigation of tooth mobility following periodontal surgery (Persson 1980), the effects on tooth mobility of gingivectomy and flap procedures were compared. A split-mouth technique was used for the two surgical procedures which were performed during one session. No preoperative differences of the investigated parameters were found. During the first weeks after surgery, an increase of tooth mobility was seen which amounted to +80% maximum (flap side) and +13.1% (gingivectomy side). The final tooth mobility changes were -60% on the flap side and -40% on the gingivectomy side. No significant differences of tooth mobility were found between the two surgical methods. The present findings of tooth mobility following surgery also indicated a considerable time lapse before any major decrease of tooth mobility took place.

Adult↗

PubMed2006

Therapeutic neovascularization by transplantation of mobilized peripheral blood mononuclear cells for limb ischemia. A comparison between CD34+ and CD34- mononuclear cells.

Autolougous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized human peripheral blood mononuclear cells (PBMNCs) improves limb ischemia in patients with arteriosclerosis obliterans of lower extremities and with diabetic foot. However, the mechanism of action of PBMNCs remains elusive. Here, we studied comparatively the effects of the G-CSF-mobilized PBMNCs and CD34-depleted G-CSF-mobilized PBMNCs in an ischemia model of athymic nude mice. Fluorescence- labeled human PBMNCs [1 x 10(6)] were intramuscularly injected into the unilateral ischemic hindlimbs of mice. Laser Doppler imaging analysis revealed a significantly augmented blood perfusion at day 7, 14 and 28 after operation. The capillary density was also markedly increased and the rate of limb loss was significantly reduced in cell-transplanted groups when compared with those in PBS group. In comparison with G-CSF-mobilized PBMNCs, the therapeutic efficiency of G-CSF-mobilized PBMNCs deprived of CD34+ cells was impaired. Transplanted cells were found to accumulate around arterioles and scatter in capillary networks. Incorporation of transplanted cells into new capillaries was observed in the G-CSF-mobilized PBMNCs group, but was not detected in the group deprived of CD34+ cells. There was an elevated expression of VEGF in ischemic tissue. Colocalization of VEGF and transplanted mononuclear cells within adductor tissue was demonstrated. These findings indicate that G-CSF-mobilized PBMNCs promote vascular growth not only by incorporating into vessel walls but also by supplying angiogenic factors. The depletion of CD34+ cells attenuated the therapeutic efficiency of G-CSF-mobilized PBMNCs in response to ischemia-induced neovascularization.

Animals↗

PubMed2003

Stem cell mobilization.

Successful blood and marrow transplant (BMT), both autologous and allogeneic, requires the infusion of a sufficient number of hematopoietic progenitor/stem cells (HPCs) capable of homing to the marrow cavity and regenerating a full array of hematopoietic cell lineages in a timely fashion. At present, the most commonly used surrogate marker for HPCs is the cell surface marker CD34, identified in the clinical laboratory by flow cytometry. Clinical studies have shown that infusion of at least 2 x 10(6) CD34(+) cells/kg recipient body weight results in reliable engraftment as measured by recovery of adequate neutrophil and platelet counts approximately 14 days after transplant. Recruitment of HPCs from the marrow into the blood is termed mobilization, or, more commonly, stem cell mobilization. In Section I, Dr. Tsvee Lapidot and colleagues review the wide range of factors influencing stem cell mobilization. Our current understanding focuses on chemokines, proteolytic enzymes, adhesion molecules, cytokines and stromal cell-stem cell interactions. On the basis of this understanding, new approaches to mobilization have been designed and are now starting to undergo clinical testing. In Section II, Dr. Michele Cottler-Fox describes factors predicting the ability to mobilize the older patient with myeloma. In addition, clinical approaches to improving collection by individualizing the timing of apheresis and adjusting the volume of blood processed to achieve a desired product are discussed. Key to this process is the daily enumeration of blood CD34(+) cells. Newer methods of enumerating and mobilizing autologous blood HPCs are discussed. In Section III, Dr. John DiPersio and colleagues provide data on clinical results of mobilizing allogeneic donors with G-CSF, GM-CSF and the combination of both as relates to the number and type of cells collected by apheresis. Newer methods of stem cell mobilization as well as the relationship of graft composition on immune reconstitution and GVHD are discussed.

Age Factors↗

PubMed2002

Enhancement of G-CSF-induced stem cell mobilization by antibodies against the beta 2 integrins LFA-1 and Mac-1.

The beta 2 integrins leukocyte function antigen-1 (LFA-1, CD11a) and macrophage antigen-1 (Mac-1, CD11b) have been reported to play a role in the attachment of CD34(+) cells to stromal cells in the bone marrow. When administered prior to interleukin-8 (IL-8), anti-LFA-1 antibodies completely prevent the IL-8-induced mobilization of hematopoietic stem cells in mice. Here, we studied the role of anti-beta 2 integrin antibodies in granulocyte colony-stimulating factor (G-CSF)-induced mobilization of hematopoietic progenitor cells. Administration of antibodies against the alpha chain of LFA-1 or against the alpha chain of Mac-1 followed by daily injections of G-CSF for more than 1 day resulted in a significant enhancement of mobilization of hematopoietic progenitor cells when compared with mobilization induced by G-CSF alone. Also, the number of late (day 28) cobblestone area-forming cells in vitro was significantly higher after mobilization with anti-LFA-1 antibodies followed by 5 microg G-CSF for 5 days than with G-CSF alone (119 +/- 34 days vs 17 +/- 14 days), indicating mobilization of repopulating stem cells. Pretreatment with blocking antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of LFA-1 and Mac-1, did not result in an effect on G-CSF-induced mobilization, suggesting that the enhancing effect required an interaction of the beta 2 integrins and one of their other ligands. Enhancement of mobilization was not observed in LFA-1-deficient (CD11a) mice, indicating that activated cells expressing LFA-1 mediate the synergistic effect, rather than LFA-1-mediated adhesion.

Animals↗

PubMed2002

Functional analysis of human hematopoietic repopulating cells mobilized with granulocyte colony-stimulating factor alone versus granulocyte colony-stimulating factor in combination with stem cell factor.

Using in vitro progenitor assays, serum-free in vitro cultures, and the nonobese diabetic/severe combined immune-deficient (NOD/SCID) ecotropic murine virus knockout xenotransplantation model to detect human SCID repopulating cells (SRCs) with multilineage reconstituting function, we have characterized and compared purified subpopulations harvested from the peripheral blood (PB) of patients receiving granulocyte colony-stimulating factor (G-CSF) alone or in combination with stem cell factor (SCF). Mobilized G-CSF plus SCF PB showed a 2-fold increase in total mononuclear cell content and a 5-fold increase in CD34-expressing cells depleted for lineage-marker expression (CD34(+)Lin(-)) as compared with patients treated with G-CSF alone. Functionally, G-CSF plus SCF-mobilized CD34(+)CD38(-)Lin(-) cells contained a 2-fold enhancement in progenitor frequency as compared with G-CSF-mobilized subsets. Despite enhanced cellularity and progenitor capacity, G-CSF plus SCF mobilization did not increase the frequency of SRCs as determined by limiting dilution analysis by means of unfractionated PB cells. Purification of SRCs from these sources demonstrated that as few as 1000 CD34(+)CD38(-)Lin(-) cells from G-CSF-mobilized PB contained SRC capacity while G-CSF plus SCF-mobilized CD34(+)CD38(-)Lin(-) cells failed to repopulate at doses up to 500 000 cells. In addition, primitive CD34(-)CD38(-)AC133(+)Lin(-) cells derived from G-CSF plus SCF-mobilized PB were capable of differentiation into CD34-expressing cells, while the identical subfractions from G-CSF PB were unable to produce CD34(+) cells in serum-free cultures. Our study defines qualitative and quantitative distinctions among subsets of primitive cells mobilized by means of G-CSF plus SCF versus G-CSF alone, and therefore has implications for the utility of purified repopulating cells from these sources.

Animals↗

PubMed2000

Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF.

PURPOSE: Patient response to hematopoietic progenitor-cell mobilizing regimens seems to vary considerably, making comparison between regimens difficult. To eliminate this inter-patient variability, we designed a cross-over trial and prospectively compared the number of progenitors mobilized into blood after granulocyte-macrophage colony-stimulating factor (GM-CSF) days 1 to 12 plus granulocyte colony-stimulating factor (G-CSF) days 7 to 12 (regimen G) with the number of progenitors after cyclophosphamide plus G-CSF days 3 to 14 (regimen C) in the same patient. PATIENTS AND METHODS: Twenty-nine patients were randomized to receive either regimen G or C first (G1 and C1, respectively) and underwent two leukaphereses. After a washout period, patients were then crossed over to the alternate regimen (C2 and G2, respectively) and underwent two additional leukaphereses. The hematopoietic progenitor-cell content of each collection was determined. In addition, toxicity and charges were tracked. RESULTS: Regimen C (n = 50) resulted in mobilization of more CD34(+) cells (2.7-fold/kg/apheresis), erythroid burst-forming units (1.8-fold/kg/apheresis), and colony-forming units-granulocyte-macrophage (2.2-fold/kg/apheresis) compared with regimen G given to the same patients (n = 46; paired t test, P<.01 for all comparisons). Compared with regimen G, regimen C resulted in better mobilization, whether it was given first (P =.025) or second (P =.02). The ability to achieve a target collection of > or =2x10(6) CD34(+) cells/kg using two leukaphereses was 50% after G1 and 90% after C1. Three of the seven patients in whom mobilization was poor after G1 had > or =2x10(6) CD34(+) cells/kg with two leukaphereses after C2. In contrast, when regimen G was given second (G2), seven out of 10 patients failed to achieve the target CD34(+) cell dose despite adequate collections after C1. Thirty percent of the patients (nine of 29) given regimen C were admitted to the hospital because of neutropenic fever for a median duration of 4 days (range, 2 to 10 days). The higher cost of regimen C was balanced by higher CD34(+) cell yield, resulting in equivalent charges based on cost per CD34(+) cell collected. CONCLUSION: We report the first clinical trial that used a cross-over design showing that high-dose cyclophosphamide plus G-CSF results in mobilization of more progenitors then GM-CSF plus G-CSF when tested in the same patient regardless of sequence of administration, although the regimen is associated with greater morbidity. Patients who fail to achieve adequate mobilization after regimen G can be treated with regimen C as an effective salvage regimen, whereas patients who fail regimen C are unlikely to benefit from subsequent treatment with regimen G. The cross-over design allowed detection of significant differences between regimens in a small cohort of patients and should be considered in design of future comparisons of mobilization regimens.

Adolescent↗

PubMed2001

Does temporary splinting before non-surgical therapy eliminate scaling and root planing-induced trauma to the mobile teeth?

The objective of this study was to determine whether temporary splinting of periodontitis-affected mobile teeth, prior to non-surgical mechanical therapy, affects treatment outcome by eliminating scaling and root planing-induced trauma to the teeth. Mandibular anterior teeth of 29 patients (15 females; 14 males; age range 30 to 48 years) with adult periodontitis were evaluated. Clinical measurements were performed at 4 sites per tooth including mesial, distal, buccal and lingual aspects at baseline, 3 and 6 months after treatment. The following clinical parameters were analyzed: plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), probing attachment level (PAL), gingival margin level (GML) and tooth mobility (TM). Patients were randomly divided into 3 groups: i) group 1 (n = 8) received scaling and root planing (SRP) only, ii) group 2 (n = 10) received scaling and root planing before splinting and iii) group 3 (n = 11) received scaling and root planing after splinting. Statistical analysis revealed that there were no significant differences among the groups for either bleeding on probing or probing attachment level values at any of the time intervals. At the end of the study, the greatest decrease in pocket depth was noted in group 2 (1.24+/-0.10 mm) which was thought to be the result of gingival recession (0.73+/-0.07 mm). Group 1 was the only group that showed reduction in tooth mobility at 3 months compared to baseline (1.67+/-0.55 PTV units). Group 3 displayed the least reduction in tooth mobility during the entire study period (0.26+/-0.44 PTV units). In conclusion, splinting of mobile teeth before SRP, and thereby elimination of potential SRP-induced trauma to the mobile teeth, did not show any adjunctive effect on healing when compared to splinting after SRP. Thorough debridement of root surfaces, even performed in the presence of increased mobility, resulted in improvements in clinical parameters, i.e. mechanical manipulation of mobile teeth during periodontal treatment did not affect clinical outcome negatively.

Adult↗

PubMed1999

Clonogenic potential and phenotypic analysis of CD34+ cells mobilized by different chemotherapy regimens.

BACKGROUND AND OBJECTIVE: Since limited data concerning quantitative and qualitative differences of CD34+ cells collected after different mobilization schedules are available, we investigated phenotype, proliferative capacity and primitive progenitor cell content of CD34+ cells mobilized with four different regimens. DESIGN AND METHODS: The number, phenotype, and progenitor cell content of CD34+ cells were investigated in 46 patients mobilized with cyclophosphamide (CY) 7 g/m(2) plus granulocyte colony-stimulating factor (G-CSF, 5 microg/kg) (CY7+G-CSF) (n=16), CY 4 g/m(2) plus G-CSF (CY4+G-CSF) (n=8), IVE [ifosphamide (2.5 g/m(2) for 3 d), etoposide (150 mg/m(2) for 3 d), epirubicin (100 mg/m(2) on day 1)] plus G-CSF (IVE+G-CSF) (n=9), or G-CSF (10 microg/kg) alone (n=13). RESULTS: The number of CD34+ cells collected per liter of processed blood was significantly higher in the CY7+G-CSF group than in the CY4+G-CSF and G-CSF groups (p </= .005), but not the IVE+G-CSF group. As compared to patients in the CY4+G-CSF group, those mobilized with CY7+G-CSF and IVE+G-CSF produced significantly lower percentages of CD34+ cells lacking CD38, CD33, CD45RA, and HLA-DR (p </= .016, at least). In addition, CY4+G-CSF mobilized CD34+ cells had a significantly higher plating efficiency than the cells mobilized in other ways (p </= r .036). In the G-CSF group, colony-forming cells and long-term culture-initiating cells were significantly lower than in the CY groups (p </= .0014 and </= 013, respectively). INTERPRETATION AND CONCLUSIONS: Our data demonstrate that: (i) different mobilization regimens allow the collection of CD34+ cells with distinct phenotypic and proliferative features; (ii) evaluation of the absolute number of CD34+ cells by itself is not a reliable indicator of the clonogenic content of blood mobilized with different chemotherapy regimens; (iii) because of the substantial impact that chemotherapy regimens have on the quantity and quality of collected CD34+ cells, anticancer effects and optimal blood progenitor cell yields should be evaluated for each chemotherapy schedule.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Combination chemotherapy containing mitoguazone, ifosfamide, methotrexate, etoposide (MIME) and G-CSF efficiently mobilize peripheral blood progenitor cells in heavily pre-treated relapsed lymphoma patients.

In this study we explored whether a standard chemotherapy regimen consisting of mitoguazone, ifosfamide, methotrexate and etoposide (MIME) combined with 5 micrograms/kg or 10 micrograms/kg G-CSF was capable of mobilizing peripheral blood progenitor cells (PBPC) in lymphoma patients. Thirty-three patients with Hodgkin's disease (HD) and 108 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3-40) of chemotherapy prior to mobilization. Eight of 141 patients failed to mobilize PBPC and bone marrow was harvested. In addition, 10 patients obtained a harvest of < 2.0 x 10(6) CD34+ cells/kg. More than 2.0 x 10(6) CD34+ cells/kg were achieved in all HD patients and in 83% of the NHL patients. Fifty-eight per cent of the patients harvested > or = 5 x 10(6) CD34+ cells/kg. Eleven per cent of the patients developed neutropenic fever during the mobilization and 3% had nadir platelet values below 20 x 10(9)/L. An inverse correlation was observed in high-grade NHL (H-NHL) patients between the number of chemotherapy cycles given before mobilization and yield of CD34+ cells. Such an association was not seen among patients with HD, transformed and low-grade NHL. When G-CSF 10 micrograms/kg was used in combination with MIME, this correlation was no longer seen in patients with H-NHL. There was also association between CD34+ cell yield and prior radiotherapy in patients with HD or transformed NHL or low-grade NHL. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF, can be successfully used to mobilize PBPC. Although no significant effect of increased dose of G-CSF was found, our data suggest that MIME/G-CSF 10 micrograms/kg should preferentially be used to mobilize PBPC in H-NHL patients pre-treated with > or = 12 cycles of chemotherapy, in irradiated HD patients and in all low-grade and transformed lymphomas.

Adolescent↗

PubMed2001

[Expression of adhesion molecules on CD34(+) hematopoietic precursor cells from normal human bone marrow, cord blood and mobilized blood].

OBJECTIVE: To investigate the expression of adhesion molecules on CD(34)(+) hematopoietic precursor cells from normal human bone marrow, cord blood and mobilized peripheral blood, and the mechanism of peripheral blood precursor cells mobilization. METHODS: CD(34)(+) hematopoietic cells were separated from bone marrow, cord blood and mobilized peripheral blood by CD(34) MultiSort Kit immunomagnetic bead system. The purity was examined by FACSort. The CD(34)(+) cells and post-short-term cultured CD(34)(+) cells were labeled in an indirect immuno-fluorescence procedure with adhesion molecules CD(11a), CD(18), CD(44), CD(49d), CD(54), CD(58) and CD(62L) monoclonal antibodies and assayed by FACSort. RESULTS: The expression of CD(11a), CD(18), CD(49d), CD(54), CD(58) and CD(62L) of mobilized peripheral blood CD(34)(+) cells was lower than that of bone marrow ones, especially for CD(49d) and CD(62L). Similar to mobilized peripheral blood CD(34)(+) cells, cord blood CD(34)(+) cells also showed a lower expression of CD(11a), CD(18), CD(44), CD(49d), CD(62L) than that of bone marrow ones, especially for CD(62L), but expression of CD(54) was higher than that of bone marrow and mobilized peripheral blood CD(34)(+) cells. CONCLUSION: The expressions of cell adhesion molecules on CD(34)(+) cells in normal bone marrow, cord blood and mobilized peripheral blood were quite different, the mechanism of peripheral blood precursors mobilization might be related to downregulation of cell adhesion molecule expression.

Antigens, CD34↗

PubMed2003

[Autologous peripheral blood stem cells mobilization with etoposide plus rhG-CSF versus cyclophosphamide plus rhG-CSF].

BACKGROUND & OBJECTIVE: It is important to get high quality autologous peripheral blood stem cell (APBSC) for successful peripheral blood stem cell transplantation. Cyclophosphamide (CTX) plus recombined human granulocyte colony-stimulating factor (rhG-CSF) is standard regimen for APBSC mobilization. Etoposide plus rhG-CSF is another regimen for mobilization in recent years. The purpose of this study was to observe and compare the effects of these two regimens in APBSC mobilization for the patients with malignant lymphoma and germ cell tumors. METHODS: Fifty-two patients were divided into two groups according to the regimen of mobilization. In CTX group, 26 patients were injected CTX 3.5 g/m(2) intravenously. The other 26 patients in VP-16 group, VP-16 1000 mg/m(2) or 1500 mg/m(2) were given intravenously at random. All patients received rhG-CSF once daily as subcutaneous injection at the dose of 5 microg x kg(-1) x day(-1) from the day of the nadir of white blood cell (WBC) till the day before the last APBSC harvest in both groups. APBSC harvest was performed daily when WBC recovered more than 2.5x10(9)/L in CTX group and 5.0x10(9)/L in VP-16 group. APBSC harvest finished when accumulated mononuclear cells (MNCs) were more than 5x10(8)/kg or CD34(+) cells were more than 2x10(6)/kg. Collected APBSC was infused following condition regimen. Blood parameters, account of harvested cells, the time of hematopoietic reconstitute, and adverse effects were compared between two groups. RESULTS: Following administration of CTX or VP-16, the nadirs of WBC and PLT in CTX group appeared significantly earlier than that in VP-16 group. The doses and times of rhG-CSF administration were not significantly different between the two groups. The start was later and the times of APBSC apheresis were less significantly in VP-16 group. The processed blood volume in single apheresis was more in VP-16 group. Speed and duration of single apheresis were similar in the two groups. Total MNCs were similar in the two groups, but the numbers of MNCs and CD34(+) cells collected in the first harvest and total number of CD34(+) cells collected were significantly more in VP-16 group. With equal quantity infusion of MNCs and CD34(+) cells infusion, hematopoietic reconstitution was achieved in both groups and the time of reconstitution was similar. Nausea and vomiting were more frequent in CTX group. Obvious PLT decrease was observed in VP-16 group. Other adverse effects were similar. CONCLUSION: CTX or VP-16 plus rhG-CSF both were safe and effective regimens for APBSC mobilization. More CD34(+) cells can be harvested by mobilization with VP-16 plus rhG-CSF than mobilization with CTX plus rhG-CSF. And the APBSC mobilized with VP-16 plus rhG-CSF can assure successful hematopoietic reconstitution.

Adolescent↗

PubMed2003

[The effect of granulocyte colony stimulating factor on T-cell subsets in peripheral blood and its correlation with the mobilization effect of CD34+ cells].

The objective was to observe the effect of G-CSF as a mobilizer of hematopoitic stem cells on the absolute counts of T-cell subsets in peripheral blood and their relevance with the mobilized CD34(+) cells. The examples of peripheral blood from 26 patients performed of autologous stem cell transplantation were taken before and after mobilization by G-CSF. Flow cytometry was used for detecting CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD4(+)CD8(+) and CD3(+)CD4(-)CD8(-) cells. Concurrently, their correlations with mobilized CD34(+) cells in peripheral blood were compared. The results showed that after the mobilization by G-CSF, the amounts of CD3(+), CD3(+)CD4(+), CD3(+)CD4(+)CD8(+) and CD3(+)CD4(-)CD8(-) cells in peripheral blood increased by 2.23, 2.62, 2.99 and 10.96 fold respectively, but that of CD3(+)CD4(-)CD8(+) cells was nearly no changed (P = 0.243). The correlation coefficient of CD3(+)CD4(-)CD8(-) cells and mobilized CD34(+) cells was 0.796, (P = 0.000) and no correlation with other T-cell subsets. It was concluded that when CD34(+) cells were mobilized by G-CSF from bone marrow to peripheral blood, the absolute counts of the peripheral T-cell subsets got changed. The increase of CD3(+)CD4(-)CD8(-) cells had correlated with mobilization effect of CD34(+) cells into peripheral blood.

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