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At least 1,189 records · Page 66Linked to original sources
PubMed2003

Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution.

BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

Acute Disease↗
PubMed2003

Tolerance of granulocyte donors towards granulocyte colony-stimulating factor stimulation and of patients towards granulocyte transfusions: results of a multicentre study.

Data of 507 granulocyte donations from 183 donors were evaluated. No severe granulocyte colony-stimulating factor (G-CSF)-related side-effects were observed. Three donors complained of severe itching following infusion of hydroxyethyl starch (HES). A high proportion (85%) of the donors stated that they would donate granulocytes again. The mean granulocyte yield was 4.3 x 10(10). High-molecular-weight HES resulted in a significantly higher yield compared with low-molecular-weight HES. Mild, but no severe, adverse transfusion reactions were observed in 16% of the recipients. A leucocyte alloimmunization rate of 24% was found. G-CSF stimulation and transfusion of G-CSF-mobilized granulocytes were well tolerated by donors and recipients, respectively.

Adolescent↗
PubMed2006

Cutaneous manifestations of granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (GCSF) is a recombinant human growth factor widely used in haematology. It is known to cause cutaneous vasculitis and neutrophilic dermatoses. We present three cases of Sweet's syndrome (SS) associated with GCSF use. Raised GCSF levels have been demonstrated in patients with SS. GCSF is the best understood mechanism by which neutrophil accumulation occurs and shows a dose-dependent effect in provoking SS.

Adjuvants, Immunologic↗
PubMed2006

Spontaneous splenic haematoma in a multiple myeloma patient receiving pegfilgrastim support.

Growth factors are a significant advance in the supportive care of patients with cancer with a wide range of indications. Frequent side effects of G-CSF include bone pain, headache, fatigue and nausea. We report a case of subcapsular splenic haematoma following pegfilgrastim administration in a 65-year old patient with multiple myeloma. Proposed mechanisms accounting for splenic enlargement include extramedullary haemopoiesis, intrasplenic infiltration by mature and immature myeloid cells and intrasplenic stem cell homing and proliferation. The risk of spontaneous splenic rupture is difficult to quantify. Physicians should be aware of this life-threatening condition and early diagnosis can be difficult since anemia and splenomegaly are common findings in haematologic patients.

Aged↗
PubMed1996

G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation.

Standard meta-analytical and pharmacoeconomic techniques were used to study the clinical effectiveness and the cost-effectiveness ratio of the prophylactic (or pre-emptive) administration of G-CSF to patients with small cell lung cancer treated with conventional myelosuppressive cytotoxic chemotherapy. In the first part of our study, we conducted a meta-analysis of the randomized clinical trials evaluating G-CSF for this clinical indication. Three trials were identified by our literature search and were included in the meta-analysis (overall number of patients = 606). The end-points for evaluating G-CSF included mortality from infection and the cumulative incidence of neutropenic fever over six cycles of chemotherapy. The results of our meta-analysis demonstrate that prophylactic G-CSF did not affect mortality but significantly reduced the incidence of neutropenic fever from 68.3% to 38.7% (pooled odds ratio = 0.29, 95% CI: 0.21-0.40; P < 0.001). In the second part of our study, we carried out a pharmacoeconomic analysis to estimate the cost-effectiveness ratio of pre-emptive G-CSF (i.e. the 'average' cost associated with the prevention of an episode of neutropenic fever). This cost-effectiveness ratio was US$ 14,372 using the Italian price of the drug converted into dollars, or US$ 41 088 using the US price. Finally, we estimated the revenue-neutral price of G-CSF based on American data of the cost-of-illness. The price ranged from US$ 395 to US$ 569 per cycle, a figure higher than the value (US$ 150) previously reported in the literature.

Antineoplastic Agents↗
PubMed2006

A single dose of 6 or 12 mg of pegfilgrastim for peripheral blood progenitor cell mobilization results in similar yields of CD34+ progenitors in patients with multiple myeloma.

BACKGROUND: Current regimens for peripheral blood progenitor cell (PBPC) mobilization in patients with multiple myeloma are based on daily subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) starting shortly after cytotoxic therapy. Recently a polyethylene glycol-conjugated G-CSF (pegfilgrastim) was introduced that has a substantially longer t(1/2) than the original formula. STUDY DESIGN AND METHODS: The use of pegfilgrastim was examined at two dose levels for PBPC mobilization in patients with Stage II or III multiple myeloma. Four days after cytotoxic therapy with cyclophosphamide (4 g/m(2)), a single dose of either 6 mg pegfilgrastim (n = 15) or 12 mg pegfilgrastim (n = 15) or daily doses of 8 microg per kg unconjugated G-CSF (n = 15) were administered. The number of circulating CD34+ cells was determined during white blood cell (WBC) recovery, and PBPC harvesting was performed by large-volume apheresis. RESULTS: Pegfilgrastim was equally potent at 6 and 12 mg with regard to mobilization and yield of CD34+ cells. No dose dependence was observed because CD34+ cell concentration peaks were 131 and 85 per microL, respectively, and CD34+ cell yield was 10.2 x 10(6) and 7.4 x 10(6) per kg of body weight, respectively. Pegfilgrastim in either dose was associated with a more rapid WBC recovery (p = 0.03) and an earlier performance of the first apheresis procedure (p < 0.05) in comparison to unconjugated G-CSF. No difference regarding CD34+ cell maximum and yield could be observed. CONCLUSION: A single dose of 6 mg pegfilgrastim is equally potent as 12 mg for mobilization and harvest of PBPCs in patients with multiple myeloma. Because no dose dependency was seen at these dose levels, this might be also true for even smaller doses.

Adult↗
PubMedDate not supplied

Pyoderma gangrenosum related to a new granulocyte colony-stimulating factor.

A 23-year-old Caucasian man diagnosed with stage IVB Hodgkin's disease was referred to a university oncology section after completing 1.5 cycles of chemotherapy. His chemotherapy consisted of doxorubicin HCL, bleomycin, dacarbazine, and vinblastine, with prophylactic administration of a granulocyte colony stimulating factor. He had developed postchemotherapy complications of possible cellulitis and necrotizing fasciitis that required wound debridement. The wound and tissue cultures were negative. Biopsies taken at the time revealed a dense inflammatory infiltrate consistent with an abscess. Over the course of 2 months, the wound healed with systemic antibiotics. The patient was reluctant to resume chemotherapy for his Hodgkin's disease because of his previous presumed skin infections. However, positive emission tomographic scanning revealed disease progression. Doxorubicin, bleomycin, dacarbazine, and prophylactic pegfilgrastim (a granulocyte colony-stimulating factor), were administered. Vinblastine was excluded from the new regimen. Shortly after chemotherapy and an injection of pegfilgrastim, the patient developed poorly defined, rapidly progressive erythema, edema, and pain in his right forearm. He presented to the emergency room, was evaluated by the orthopedics service, and taken to the operating room for debridement of suspected necrotizing fasciitis. When the dermatology service consulted the following day, the patient had developed an erythematous, edematous, tender plaque on his chest. After developing two additional lesions that began to ulcerate despite treatment with imipenem, vancomycin, clindamycin, rifampin, and gentamicin, the patient consented to a skin biopsy. His wound cultures continued to be negative.

Adult↗
PubMed1999

Early establishment of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantation.

To characterize the process of the establishment of complete chimerism after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), we determined the origin of leukocytes in peripheral blood (PB) obtained from 23 patients in the very early period after allo-PBSCT using amplification of mini- or microsatellite regions of genomic DNA. Donor-specific alleles were amplified from the PB obtained at day 8 post-transplant for 19 allo-PBSCT patients. Among the 19 patients, 12 showed only donor-specific alleles (complete chimerism) while 7 did both donor and host-specific alleles (mixed chimerism). Although donor specific alleles were amplified in 10 of 12 patients who received allogeneic bone marrow transplantation (allo-BMT) similarly to allo-PBSCT, all of these ten showed mixed chimerism. When the chimeric state was examined in PB samples obtained serially at 2-3-day intervals post-transplant, host-specific alleles in allo-PBSCT patients were not detectable in the PB much earlier than those in allo-BMT patients. These findings indicate that the appearance of donor-derived cells associated with the disappearance of host-derived cells in the circulation occurs earlier after allo-PBSCT as compared with allo-BMT, leading to the rapid establishment of complete chimerism.

Adolescent↗
PubMed2000

Angiotensin II increases host resistance to peritonitis.

Studies by other laboratories have shown that angiotensin II (AII) can affect the function of cells which comprise the immune system. In the present study, the effect of AII on the function of peritoneal macrophages and peripheral blood monocytes was assessed. In vitro exposure (4 h prior to assay) of peritoneal macrophages from mice and rats to AII increased the percentage of cells that phagocytosed opsonized yeast and the number of yeast per macrophage. Furthermore, AII increased the respiratory burst capacity of peritoneal macrophages from mice and rats and peripheral blood mononuclear cells from humans. Because of these observations, the effect of AII on host resistance to bacterial infection was assessed. Intraperitoneal administration of AII was shown to increase host resistance (reduced abscess formation) in an animal model of bacterial peritonitis. Studies were then conducted to assess whether parenteral administration of AII, a clinically relevant route, could affect peritoneal host resistance in a manner similar to that observed after peritoneal administration. These studies showed that subcutaneous administration of AII throughout the postinfection interval increased the level of host resistance to bacterial peritonitis. Furthermore, in a study which compared AII and Neupogen, an agent approved for use for the reduction of febrile neutropenia after myeloablative therapy, daily subcutaneous administration of AII reduced abscess size and incidence, whereas Neupogen did not have any therapeutic benefit in this model. These data suggest that AII may be of therapeutic benefit as an immunomodulatory agent.

Angiotensin II↗
PubMed2000

Long-term hematopoietic engraftment after autologous peripheral blood progenitor cell transplantation in pediatric patients: effect of the CD34+ cell dose.

BACKGROUND AND OBJECTIVES: We analyzed the relationship between long-term hematopoietic recovery and the number of CD34+ cells infused in order to determine the optimal dose of CD34+ cells for rapid and stable engraftment. PATIENTS AND METHODS: Between November 1993 and December 1998, 96 consecutive autologous transplantations were performed in 92 pediatric patients with different malignancies. Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF alone (12 microg/kg/day s.c., Neupogen((R)); Amgen, Thousand Oaks, Calif., USA) and collected using a Cobe Spectra blood cell separator (Cobe, Denver, Colo., USA) through a central venous catheter with double lumen. The CD34+ cell contents of apheresis products were assessed by means of flow-cytometric analysis using an Epics Elite flow cytometer (Coulter, USA). RESULTS: The median number of CD34+ cells infused was 3.2 x 10(6)/kg (range 0.17-44.4). The median times for short-term engraftment (neutrophil count >0.5 x 10(9)/l and platelet count >20 x 10(9)/l) was 9 (range: 7-16) and 13 days (range: 7-91), respectively. The median times for long-term engraftment (platelet count >50 x 10(9)/l and >100 x 10(9)/l) was 21 (range: 10-249) and 45 days (range: 12-288). When the infused CD34+ cell dose was >/=5 x 10(6)/kg (median 7.99, range 5.01-44.4), there was a statistically significant increase in the rate of short- and long-term hematopoietic recovery compared to patients transplanted with a lower number of CD34+ cells (p < 0.0001). The earlier recovery in the high CD34+ cell group resulted in less transfusional support, fewer days on intravenous antibiotics and shorter hospitalization. CONCLUSIONS: This study confirms that G-CSF-mobilized PBPC provide rapid short- and long-term hematopoietic engraftment in pediatric patients undergoing autologous transplantation if a CD34+ cell dose >/=5.0 x 10(6)/kg is infused. As this PBPC dose seems to have clinical and potentially economic implications, it should be considered the optimal dose for apheresis.

Adolescent↗
PubMed2001

Autologous hematopoietic stem cell transplantation in chronic myeloid leukemia with different clinical stages.

Seven patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) were treated with an ICE-based regimen plus G-CSF with the aim of mobilizing and collecting Ph-negative peripheral stem cells in the setting of an autologous transplant program. Five patients had CML in the first chronic phase and 2 in the accelerated phase. All patients had been previously treated with interferon-alpha. Median value and ranges for harvested mononuclear cells, CD34+ cells and CFU-GM, respectively: 5.65 x 10(8)/kg (2.61-11.38); 1.48 x 10(6)/kg (0.216-3.5), and 3.43 x 10(4)/kg (0.243-11.6). FISH was the only useful method for detection of minimal residual disease on apheresis product showing <5% t(9;22) positive cells in 2 cases and <10% positive cells in 4 other cases. Four of seven autologous grafts have been transplanted to date. Busulfan conditioning was used in 1 case and TBI/Cy conditioning in 3 other cases. All patients are alive and well following transplantation and are on interferon-alpha therapy.

Adult↗
PubMedDate not supplied

Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report.

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study, we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve patients with distant metastatic disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle, 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients, 6 of whom had received previous treatment. There were 2 deaths due to toxicity, and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up, only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients, bone marrow suppression is still the major limiting toxic side effect of aggressive chemotherapy, especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support.

Adult↗
PubMed2004

Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease.

OBJECTIVE: Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. METHODS AND RESULTS: Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063% versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+) cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006% MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05) or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for 5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/-10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/-0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a decline to 9+/-4/well at 2 weeks (P=0.06). CONCLUSIONS: Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair in coronary artery disease patients must be tested in clinical trials.

AC133 Antigen↗
PubMed2006

Pharmacokinetic/pharmacodynamic modeling of pegfilgrastim in healthy subjects.

This analysis was conducted to characterize the pharmacokinetics and pharmacodynamics of pegfilgrastim and to develop a pharmacokinetic-pharmacodynamic model to describe the granulopoietic effects of pegfilgrastim and the homeostatic regulation of pegfilgrastim clearance in healthy subjects. Pegfilgrastim serum concentration data and differential white cell counts were obtained from an open-label, single-dose, dose escalation study. Healthy subjects (8 subjects/dose group) received a single subcutaneous dose of 30, 60, 100, or 300 microg/kg pegfilgrastim. Pegfilgrastim exhibited nonlinear pharmacokinetics; clearance decreased with increasing dose. A dose-dependent increase in absolute neutrophil count with an increase in the percentage of band cells was observed. A pharmacokinetic-pharmacodynamic model was developed that adequately described the nonlinear pharmacokinetics of pegfilgrastim, feedback regulation of pegfilgrastim clearance by neutrophils, and the differential effects of pegfilgrastim on neutrophil populations in blood.

Cell Proliferation↗