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At least 1,045 records · Page 58Linked to original sources
PubMed1997

Predictors for optimal mobilization and subsequent engraftment of peripheral blood progenitor cells following intermediate dose cyclophosphamide and G-CSF.

Fifty consecutive patients undergoing cyclophosphamide/G-CSF mobilization were studied for indicators predictive for adequate harvest (CD34+ cells > 2 x 10(6)/kg, CFU-GM > 1 x 10(5)/kg). Target yields following a single leukopheresis were achieved for 66% of patients (89% with no previous alkylation chemotherapy or radiotherapy). Previous alkylation therapy, radiotherapy and low collection day platelet count were predictive of poor collection yields. Following reinfusion, the median time to platelets > 20 x 10(9)/l (PLT > 20) was 10 days and to neutrophils > 500 x 10(6)/l (ANC > 500) was 13 days. Total CD34+ cells infused was predictive of early platelet engraftment. Previous radiotherapy was inversely predictive of neutrophil engraftment. For the majority of patients not exposed to alkylation therapy or radiotherapy, adequate progenitor cells can be collected following a single leukopheresis. In patients suitable for future autologous bone marrow transplantation it would seem appropriate to avoid or minimize radiotherapy and alkylation therapy exposure in the pre-collection period.

Adolescent↗
PubMed1997

Subcutaneous T-cell lymphoma treated with systemic chemotherapy, autologous stem cell support, and limb amputation.

Subcutaneous T-cell lymphoma is an unusual variant of peripheral T-cell lymphoma in which the malignant infiltrate preferentially involves the subcutis. The disease is often initially misdiagnosed as a benign inflammatory panniculitis or a granulomatous disease. We describe subcutaneous T-cell lymphoma in a 39-year-old man who was treated with systemic chemotherapy, autologous stem cell support, and amputation of the limb primarily involved with the lymphomatous infiltrate. This is the first report of amputation being included in the treatment regimen of subcutaneous T-cell lymphoma. Because preferential involvement of the extremities often occurs in patients with subcutaneous T-cell lymphoma, surgical debulking of refractory disease by partial or complete limb amputation may be a useful therapeutic adjunct.

Adult↗
PubMed2000

[Do hematopoietic growth factors have a role in the treatment of drug-induced agranulocytosis?].

PURPOSE: Our study was aimed at determining the role of hematopoietic growth factor in drug-induced agranulocytosis. METHODS: Fifty-five cases of drug-induced agranulocytosis were reviewed and subdivided retrospectively into a G-CSF group (n = 15) and an untreated group (n = 40). Mortality and hematological recovery (number of days required for neutrophil counts to exceed 1.5 x 10(9)/L) were studied in the two groups. RESULTS: The mean granulocyte count was 0.09 x 10(9)/L. All patients presented infection. In the G-CSF group, no mortality (0% versus 5%, P = 0.85) and a shorter recovery time (8.1 versus 9.5 days P = 0.39) were observed. No significant difference between the two groups was observed in either the duration of antibiotic therapy (9.3 days in the G-CSF group versus 10.1 days in the untreated group, P = 0.51) or duration of hospitalization (10 days in the treated group versus 11 days in the G-CSF group, P = 0.46). CONCLUSION: Our results as well as a literature review indicate that G-CSF could decrease the time to hematological recovery and perhaps reduce mortality. However, the exact role of hematopoietic growth factors requires further investigations.

Aged↗
PubMed2001

[Ecthyma gangrenosum caused by Pseudomonas aeruginosa without septicemia in a neutropenic patient].

INTRODUCTION: Ecthyma gangrenosum is a rare skin infection caused by gram negative bacteria. It involves immunocompromised patients, especially neutropenic patients, and can be easily diagnosed. EXEGESIS: We report a case of ecthyma gangrenosum without septicemia due to Pseudomonas aeruginosa in a myelodysplastic patient with severe neutropenia. Granulocyte growth factors adjunction was necessary in combination to antibiotics to obtain complete healing. CONCLUSION: In neutropenic patient, ecthyma gangrenosum due to Pseudomonas aeruginosa should be rapidly diagnosed to avoid septicemic complications. In the case of antibiotic treatment failure, granulocyte growth factors may be added. Frequent Pseudomonas aeruginosa infections justify bacteriologic survey to look for hospital contamination.

Aged↗
PubMed2001

Stem cell factor prevents Fas-mediated apoptosis of human erythroid precursor cells with Src-family kinase dependency.

The Fas ligand (Fas-L) expressed on mature erythroblasts may induce apoptosis of more immature erythroid cells that express Fas, whereas stem cell factor (SCF) may prevent Fas-mediated cell death in hematopoietic progenitor cells. The manner in which SCF prevents Fas-mediated cell death still is unclear. Given the essential role of SCF and the potentially important involvement of the Fas/Fas-L system in the development of erythrocytes, we studied mechanisms related to SCF prevention of Fas-mediated apoptosis. We used primary cultured human erythroid colony-forming cells (ECFC) derived from CD34+ cells and enriched glycophorin A positive (GPA+) c-kit+ cells in ECFC. Apoptosis of ECFC was induced by an Fas-L mimetic monoclonal antibody CH11. DNA fragmentation and the activation of caspase-3 and caspase-8 were measured using commercially available kits. Characterization of expanded cells was performed using multiparameter flow cytometry. Lyn kinase activity was measured by enolase kinase assays. SCF inhibited the CH11-induced DNA fragmentation of ECFC as well as enriched GPA+ c-kit+ cells in ECFC, but not those of GPA+ c-kit- cells. SCF also inhibited the activation of caspase-3 and caspase-8, without downregulation of the surface expression of Fas, suggesting that SCF prevents apoptosis through uncoupling of Fas ligation from subsequent caspase activation. PP2, a specific inhibitor of Src-family kinases, antagonized the effects of SCF in preventing Fas-mediated apoptosis. We propose that SCF prevents Fas-mediated apoptosis of erythroid progenitor cells in a manner dependent on the activity of Src-family tyrosine kinases. We also identified active Lyn in erythroid cells. These data suggest the presence of a novel Src-family-dependent function of SCF in the development of erythrocytes.

Antibodies, Monoclonal↗
PubMed2002

Tumor necrosis factor-alpha inhibits generation of glycophorin A+ cells by CD34+ cells.

OBJECTIVE: The inhibitory effects of tumor necrosis factor-alpha (TNF-alpha) on cytokine-induced proliferation and differentiation of normal human erythroid progenitors have been characterized extensively, yet little is known about the maturation level of erythroid progenitors that are sensitive to TNF-alpha or of the expression of TNF receptors (TNFRs) in erythroid lineage. The aim of this study was to determine the extent to which human erythroid progenitor cells are sensitive to TNF-alpha, and to relate this to the expression of TNFRs in the erythroid lineage. MATERIALS AND METHODS: Highly purified human CD34+ cells underwent erythroid differentiation, with or without TNF-alpha. We used colony assay as well as a method by which colony-forming unit-erythroid (CFU-E) and glycophorin A (GPA; a specific marker for erythroid lineage) positive cells can be generated in liquid phase from purified human CD34+ cells in the presence of multiple cytokines, including stem cell factor (SCF), interleukin-3 (IL-3), and erythropoietin (EPO). During erythroid differentiation of CD34+ cells, TNFRs expression were monitored. RESULTS: TNF-alpha inhibited the generation of GPA+ cells by CD34+ cells as well as the proliferative capacity of GPA+ cells supported by EPO, IL-3, and SCF. Erythroid progenitors became resistant to the inhibitory effect of TNF-alpha as they matured. The detectable expression of TNFR-I was transient in the early phase of erythroid differentiation, whereas TNFR-II was expressed through the entire course of erythroid differentiation of CD34+ cells. CONCLUSIONS: TNF-alpha suppresses erythropoiesis by inhibiting the generation of GPA+ cells derived from CD34+ cells as well as by inhibiting the proliferative capacity of GPA+ cells. Although the presence of TNFRs does not directly indicate that the receptor(s) mediates death signaling, altered expression of TNFRs depending on the level of maturation may imply altered sensitivities to TNF-alpha in various stage of erythroid progenitors.

Adult↗
PubMed1999

Occurrence of periodic oscillations in the differential blood counts of congenital, idiopathic, and cyclical neutropenic patients before and during treatment with G-CSF.

Using techniques developed in astrophysics to deal with unequally sampled data sets, we have analyzed serial differential cell counts from 45 congenital, idiopathic, and cyclic neutropenic patients before and during treatment with recombinant human G-CSF (rhG-CSF). Our results show that the occurrence of significant cycling in the absolute neutrophil count (ANC) of neutropenics not classified as cyclical is much more prevalent than had been previously thought, and that not all the patients classified as cyclic show significant ANC periodicity. In these patients, cycling in more than one cell line may be involved. The range of periods encountered in these patients is much broader (between 11 and 52 days) than is usually associated with classical cyclical neutropenia, and there is no obvious connection between the range of periods and the patient's diagnostic category. Administration of rhG-CSF is able to induce significant cycling in neutropenic patients that were not cycling prior to treatment. In patients who had significant cycling before treatment, rhG-CSF may either decrease the period to between 11 and 14 days, or may obliterate any statistical evidence of cycling.

Adult↗
PubMed1999

Myelopoietin, a chimeric agonist of human interleukin 3 and granulocyte colony-stimulating factor receptors, mobilizes CD34+ cells that rapidly engraft lethally x-irradiated nonhuman primates.

Myelopoietin (MPO), a multifunctional agonist of interleukin 3 and granulocyte colony-stimulating factor (G-CSF) receptors, was evaluated for its ability to mobilize hematopoietic colony-forming cells (CFC) and CD34+ cells relative to control cytokines in normal nonhuman primates. Additionally, the engraftment potential of MPO-mobilized CD34+ cells was assessed in lethally irradiated rhesus monkeys. Normal rhesus monkeys were administered either MPO (200 microg/kg/day), daniplestim (a high-affinity interleukin 3 receptor agonist) (100 microg/kg/day), G-CSF (100 microg/kg/day), or daniplestim coadministered with G-CSF (100 microg/kg/day each), subcutaneously for 10 consecutive days. The mobilization kinetics were characterized by peripheral blood (PB) complete blood counts, hematopoietic CFC [granulocyte-macrophage CFC (GM-CFC), megakaryocyte CFC (MK-CFC)], and the immunophenotype (CD34+ cells) of PB nucleated cells prior to and on day 3 to days 7, 10, 12, and 14, and at intervals up to day 28 following initiation of cytokine administration. A single large-volume leukapheresis was conducted on day 5 in an additional cohort (n = 10) of MPO-mobilized animals. Eight of these animals were transplanted with two doses of CD34+ cells/kg. A maximum 10-fold increase in PB leukocytes (white blood cells) (from baseline 7.8-12.3 x 10(3)/microL to approximately 90 x 10(3)/microL) was observed over day 7 to day 10 in the MPO, G-CSF, or daniplestim+G-CSF cohorts, whereas daniplestim alone stimulated a less than onefold increase. A sustained, maximal rise in PB-derived GM-CFC/mL was observed over day 4 to day 10 for the MPO-treated cohort, whereas the daniplestim+G-CSF, G-CSF alone, and daniplestim alone treated cohorts were characterized by a mean peak value on days 7, 6, and 18, respectively. Mean peak values for PB-derived GM-CFC/mL were greater for MPO (5,427/mL) than for daniplestim+G-CSF (3,534/mL), G-CSF alone (3,437/mL), or daniplestim alone (155/mL) treated cohorts. Mean peak values for CD34+ cells/mL were noted within day 4 to day 5 of cytokine administration: MPO (255/microL, day 5), daniplestim+G-CSF (47/microL, day 5), G-CSF (182/microL, day 4), and daniplestim (96/microL, day 5). Analysis of the mobilization data as area under the curve indicated that for total CFCs, GM-CFC, MK-CFC, or CD34+ cells, the MPO-treated areas under the curve were greater than those for all other experimental cohorts. A single, large-volume (3.0 x blood volume) leukapheresis at day 5 of MPO administration (PB: CD34+ cell/microL = 438 +/- 140, CFC/mL = 5,170 +/- 140) resulted in collection of sufficient CD34+ cells (4.31 x 10(6)/kg +/- 1.08) and/or total CFCs (33.8 x 10(4)/kg +/- 8.34) for autologous transplantation of the lethally irradiated host. The immunoselected CD34+ cells were transfused into autologous recipients (n = 8) at cell doses of 2 x 10(6)/kg (n = 5), and 4 x 10(6)/kg (n = 3) on the day of apheresis. Successful engraftment occurred with each cell dose. The data demonstrated that MPO is an effective and efficient mobilizer of PB progenitor cells and CD34+ cells, such that a single leukapheresis procedure results in collection of sufficient stem cells for transplantation and long term engraftment of lethally irradiated hosts.

Animals↗
PubMed1996

Neurobiochemical changes from Taxol/Neupogen chemotherapy for metastatic breast carcinoma corresponds with suicidal depression.

A patient under Taxol and granulocyte colony stimulating factor (G-CSF, Neupogen) treatment for metastatic breast carcinoma of the liver experienced repeated suicidal depression on days 10 and 11 of therapy. MRI and MRS were performed during the fifth and sixth cycles of chemotherapy on days 1 and 10. The MRI was normal in all four examinations. The MRS showed normal levels of metabolites on days 1 of therapy, with remarkable reproducible declines in neurobiochemicals myo-inositol (23-27%), choline (20-24%), creatine (10-14%) and glutamate/glutamine (22-39%) on day 10 of therapy. The neurobiochemical declines coincided with the patient's experience of suicidal depression. Patients reporting depression during standard cancer therapy may be experiencing previously undocumented chemotherapeutic neurobiochemical imbalances or neurotoxicity.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Pegylation: engineering improved pharmaceuticals for enhanced therapy.

Conjugating biomolecules with polyethylene glycol (PEG), a process known as pegylation, is now an established method for increasing the circulating half-life of protein and liposomal pharmaceuticals. Polyethylene glycols are nontoxic water-soluble polymers that, owing to their large hydrodynamic volume, create a shield around the pegylated drug, thus protecting it from renal clearance, enzymatic degradation, and recognition by cells of the immune system. Agent-specific pegylation methods have been used in recent years to produce pegylated drugs that have biologic activity that is the same as, or greater than, that of the parent drug. These agents have distinct in vivo pharmacokinetic and pharmacodynamic properties, as exemplified by the self-regulated clearance of pegfilgrastim, the prolonged absorption half-life of pegylated interferon alpha-2a, and the altered tolerability profile of pegylated liposomal doxorubicin. Pegylated agents have dosing schedules that are more convenient and more acceptable to patients, and this can have a beneficial effect on the quality of life of patients with cancer.

Antineoplastic Agents↗
PubMed1998

Oxidation of recombinant methionyl human granulocyte colony stimulating factor.

The oxidation of methionine residues in recombinant methionyl human granulocyte colony stimulating factor with hydrogen peroxide has been investigated. Kinetic data of the oxidation were obtained by using reversed phase-high performance liquid chromatography. The stability-indicating capability of this system was confirmed with micellar electrokinetic capillary chromatography. In the pH range 1.9-7.5, the kobs value for the oxidation process is constant. Above pH 7.5, kobs tends to increase with increasing pH. In the pH range 1.9-11.8, four oxidation products were detected in RP-HPLC. Mass spectrometric analysis revealed that one mono-, one di- and two trioxidation products were formed. Using the cyanogen bromide cleavage method the nature of the oxidation products was determined. The mono-oxidation product is the protein with Met121 oxidized, while the dioxidation product has oxidized Met121 and Met126 residues. The trioxidation products are the proteins with Met121, Met126 and Met137 or Met0, Met121 and Met126 oxidized.

Amino Acid Sequence↗
PubMed2001

Induction therapy of adult acute lymphocytic leukemia without the use of vincristine or prednisone.

In the last 30 years, a multitude of treatment regimens for adult acute lymphocytic leukemia (ALL) has been developed. Essentially, all of these regimens use an induction therapy vincristine, prednisone, and an anthracycline intensified with L-asparaginase or cyclophosphamide. Though such regimens induce most patients to enter a remission, relapse is frequent, and most adult patients ultimately die of their disease. The author postulated that further refinements in this approach to induction therapy were unlikely to markedly improve treatment results in this disease. Therefore, the author is studying a new intensive strategy using cytarabine with a single very high dose of mitoxantrone (without vincristine or prednisone) as induction therapy for adult patients with ALL.

Adolescent↗
PubMed1997

G-CSF-induced mobilization of peripheral blood stem cells for allografting: comparative study of daily single versus divided dose of G-CSF.

We conducted a comparative study on a daily single versus a divided dose of G-CSF for G-CSF-induced mobilization of peripheral blood stem cells (PBSC) in eleven HLA-identical sibling donors of allogeneic PBSC transplantation (PBSCT). Six donors received double subcutaneous injections of G-CSF at a dose of 5 micrograms/kg x 2/day for 5 days (Group A), while the remaining five received single subcutaneous injection at a dose of 10 micrograms/kg/day for 5 days (Group B). The numbers of circulating CD34+ cells, myeloid progenitors (CFU-GM) and erythroid progenitors (BFU-E) reached peak values at day 5 of G-CSF administration in both groups. The mean number of CD34+ cells harvested per apheresis was 4.4 x 10(6)/kg (cells/body weight of each donor, range: 0.8-7.9 x 10(6)/kg) in Group A and 5.1 x 10(6)/kg (range: 3.0-9.0 x 10(6)/kg) in Group B. There were no significant differences between these two groups in total numbers of CFU-GM, BFU-E, or T-lymphocytes harvested. Adverse effects including mild to moderate bone pain and thrombocytopenia were transient and well tolerated. No difference was observed in the incidence of adverse effects between the two groups. These observations suggest that there is no difference in G-CSF-induced mobilization of PBSC between daily single and divided dose of G-CSF to collect a sufficient number of PBSC for engraftment after allo-PBSCT.

Adolescent↗
PubMed1997

Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian Sarcoma Group Phase II Study.

The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.

Adolescent↗
PubMed1997

Tandem high-dose therapy with ifosfamide, epirubicin, carboplatin and peripheral blood stem cell support is an effective adjuvant treatment for high-risk primary breast cancer.

We evaluated the therapeutic efficacy and toxicity of a tandem high-dose therapy with peripheral blood stem cell (PBSC) support in 40 patients with high-risk, primary breast cancer (stage II-III) and involvement of ten or more positive axillary lymph nodes. Their median age was 44 years (range 23-56). Two cycles of cytotoxic chemotherapy with ifosfamide (10000 mg/m2) and epirubicin (100 mg/m2) were administered. Granulocyte colony-stimulating factor (G-CSF) was given to hasten neutrophil reconstitution and to mobilise PBSC during marrow recovery. Leukaphereses were performed following the first and/or second cycle. Tandem high-dose therapy consisted of two cycles with ifosfamide (15 or 12 g/m2) and epirubicin (150 mg/m2), while carboplatin (900 mg/m2) was added for the last 24 patients included. Using an immunocytochemical method, two of 11 patients had cytokeratin-positive tumour cells in three leukapheresis products that were collected following the first G-CSF-supported cycle with ifosfamide and epirubicin, whereas only two harvests obtained following the second cycle in 26 patients contained cytokeratin-positive tumour cells. The number of CD34+ cells/kg re-infused following both high-dose cycles was similar (4.20 +/- 0.29 x 10(6), first cycle and 5.25 +/- 0.63 x 10(6), second cycle), and no notable difference was noted in the speed of haematological reconstitution. An absolute neutrophil count (ANC) of 0.5 x 10(9)/1 was reached after a median time of 13 days, while an unsupported platelet count of 20.0 x 10(9)/1 was achieved after a median time of 8 (first cycle) and 9 (second cycle) days post-transplantation. Patients autografted with more than 7.5 x 10(6) CD34+ cells/kg had platelet counts above 20 x 10(9)/1 within less than 10 days. 6 patients relapsed between 7 and 11 months (median 8 months) post-transplantation. 37 patients are alive and in remission with a median follow-up time of 11 months (range 1-38). This translates into a probability of disease-free survival (DFS) of 77% (95% CI 32-95%) at 38 months. The probability of overall survival is 85%, since 3 patients with local relapse achieved a second complete remission following surgery and involved-field radiotherapy. In conclusion, a sequential high-dose therapy including ifosfamide, epirubicin, carboplatin and PBSC support is well tolerated and effective in patients with high-risk primary breast cancer. Involved-field irradiation should be performed post-transplantation to reduce the risk of local relapse.

Adult↗
PubMed1996

Comparison of the content and subpopulations of CD3 and CD34 positive cells in bone marrow harvests and G-CSF-mobilized peripheral blood leukapheresis products from healthy adult donors.

Recombinant human granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem/progenitor cells (PBPC) have replaced bone marrow (BM) harvests for autologous transplantation after myeloablative therapy in cancer patients. G-CSF-mobilized PBPC from healthy donors contain one log excess of T lymphocytes representing a potential risk for graft-versus-host disease (GVHD). However, recent pilot clinical studies of G-CSF-mobilized allogeneic PBPC transplantation have shown rapid haematological recovery and no severe acute GVHD except in a very few cases. Therefore, the risk of inducing severe acute GVHD is not as high as was expected during the pioneering period of allogeneic PBPC transplantation. The present study was performed to address the possible reasons for the rapid haematological recovery and the absence of severe acute GVHD observed after allogeneic PBPC transplantation by comparing the contents and subsets of CD3+ and CD34+ G-CSF-mobilized PBPC (n = 31) with those of BM (n = 26) allografts from healthy adult donors. The present results revealed that the phenotypic profiles of CD3+ and CD34+ cells differ between PBPC and BM allografts. The single PBPC leukapheresis product contained 10 times more mononuclear cells, 1.5 times more CD34+ cells, 5.5 times more CD3+ T lymphocytes, 3 times more CD19+ B lymphocytes and 3.8 times more CD14+ monocytes than the single BM harvest. Both CD34+CD33+ myeloid progenitor cells and CD34+HLA-DR-long-term reconstituting haemopoietic stem cells were significantly increased in the CD34+ G-CSF-mobilized PBPC compared with the CD34+ BM cells; median 73.1% and 30.4% vs 60.6% and 5.0%, respectively, P < 0.01. The percentage of CD3+ cells coexpressing CD4 (T helper/inducer) was similar in both PBPC and BM allografts, 47.2% and 45.6%, respectively, whereas the percentage of CD3+ cells coexpressing CD8 (T suppressor/cytotoxic) was significantly decreased in PBPC compared with BM; 37.0% vs 55.9%, p < 0.01. The rapid haematological recovery after allogeneic PBPC transplantation could be due to the increased content of CD34+CD33+ myeloid committed cells and the CD34+HLA-DR-long-term reconstituting haemopoietic stem cells in the PBPC allografts. Also, the absence of an increased risk of severe acute GVHD after allogeneic PBPC transplantation could be due to the increased T lymphocyte ratio of CD4+/CD8+ in the PBPC allografts. In conclusion, rapid haematological recovery without an increased risk of severe acute GVHD can be achieved using G-CSF-mobilized PBPC rather than BM for allogeneic transplantation.

Adult↗