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At least 1,279 records · Page 71Linked to original sources
PubMed2003

[Acute respiratory distress syndrome due to pneumonitis following intrathecal methotrexate administration].

INTRODUCTION: Methotrexate, given orally or systemically, is associated with pneumonitis in 7% of cases. CASE REPORT: This case report describes acute respiratory distress syndrome, due to diffuse pneumonitis, in a patient with malignant non-Hodgkin's lymphoma being treated with combination chemotherapy which included doxorubicin, cyclophosphamide, bleomycin, vindesin and intrathecal methotrexate with G-CSF (filgrastine- Neupogen). The clinical course, the lack of an identifiable infectious agent and the complete response to corticosteroids suggested a drug-induced cause. After ruling out the other chemotherapy agents, methotrexate was considered to be the causal agent. The unusual feature of this case was that pneumonitis developed after intrathecal administration of methotrexate. CONCLUSION: Methotrexate-associated respiratory complications can occur with whichever route the drug is administered.

Anti-Inflammatory Agents↗
PubMed2003

[Analysis of phenotypes and kinetics of CD34+ cells and lymphocytes in donors of hematopoietic stem cells for allogenic transplantation].

BACKGROUND: Amount of CD34+ cells is a critical parameter for quality assessment and successful engraftment of peripheral blood hematopoietic stem cells (PBSC) during the transplantation of haemopoisis. CD34+ cells are routinely analysed by immunophenotyping in PBSC and in peripheral blood during mobilization. Other leukocyte subpopulations are not usually assessed. METHODS AND RESULTS: The authors present results of immunophenotyping of subpopulations of CD34+ cells and leucocytes in samples from donors of PBSC for allogeneic transplantations, who were stimulated with the growth factor G-CSF at dose 16 micrograms/kg/day. The amount of CD34+ cells was not significantly different between days 4 and 5; however, there was a significant drop at day 6. CD34+90+ and CD34+61+ subpopulations reached their maximum at the day 4; partially differentiated CD34+ cells with co-expression of CD33, CD19, and CD7 reached maximum at the day 6. CD4+ Th-lymphocytes were concentrated in the grafts during leukapheresis, CD4/CD8 ratio in the grafts was increased to average 3.06. CONCLUSIONS: The knowledge of kinetics of CD34+ subpopulations, together with stem cell selection and ex vivo manipulation, may have an impact on the speed of engraftment or GvHD prevention in transplanted patients.

Antigens, CD34↗
PubMed2003

Detection of myelodysplastic syndrome/ acute myeloid leukemia evolving from aplastic anemia in children, treated with recombinant human G-CSF.

BACKGROUNDS AND OBJECTIVES: Recombinant human granulocyte colony-stimulating factor (G-CSF) has clear benefits in patients with severe neutropenia. However, recent reports of myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) developing after treatment with immunosuppressants and G-CSF has raised concern over the use of this agent in patients with aplastic anemia. DESIGN AND METHODS: We undertook a multi-institutional, non-randomized study of 112 children given a diagnosis of aplastic anemia, and then treated with different immunosuppressants with or without G-CSF. In each case, bone marrow specimens were tested at study entry and every 6 months for 3 years to detect t-MDS/AML, defined by stringent morphological and molecular/cytogenetic criteria. Incidence rates were calculated by the person-years statistical method. RESULTS: As of December 2001, all eligible patients had been followed for a median of 3 years, and the G-CSF (+) group had received a median total G-CSF dose of 30,100 micrograms altogether, administered over a median of 4 months. Only one case of MDS developed among the G-CSF (+) patients (n=81), compared with three in the group receiving other agents (n=31). This isolated case was not associated with monosomy 7, the cytogenetic abnormality most often linked to G-CSF treatment. Incidence rates of MDS in the two groups were not significantly different (3.8 vs. 22.4 per 1,000 patient-years at risk, p=0.125). There were no cases of overt AML in either cohort. INTERPRETATION AND CONCLUSIONS: G-CSF therapy did not increase the risk of t-MDS/AML development in children with aplastic anemia over a median follow-up of 3.7 years

Acute Disease↗
PubMed2004

Polymer therapeutics - Sixth International Symposium: from laboratory to clinical practice. Industrial development and clinical evaluation.

This biannual conference was organized, as is now customary, by Professor Ruth Duncan of the Welsh School of Pharmacy and focused on novel technology and pharmaceutical compounds in the area of polymer therapeutics. This meeting has established itself as an important interface between discovery research and preclinical and clinical development in this field. Sufficient time was allocated for informal interaction between the delegates, which allowed for plenty of discussion and initiation of collaboration. The emphasis in most presentations was on the use of polymers and dendrimers as active ingredients, or for conjugation with other entities for the purpose of improving drug properties such as pharmacodynamic (PD) and pharmacokinetic (PK) profile, drug handling, or targeting and delivery. Several talks and posters focused on novel and proven techniques for the biophysical characterization of polymer constructs and their metabolites. To date, the most successful therapeutic class are conjugates of polymers to protein drugs; six drugs are approved and approximately a dozen are in various stages of clinical development. However, several covalent and non-covalent conjugates of small-molecule cancer chemotherapy agents are now in more advanced clinical trials, and several other polymer constructs and dendrimers are in early clinical trials. This meeting clearly demonstrated that there are many promising approaches for the application of a variety of polymers, but that the viability of many of the approaches still needs to be proven in late-stage clinical trials as well as in the market place.

Animals↗
PubMed2004

Economic evaluation of prophylactic granulocyte colony stimulating factor during chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: Treatment with CHOP chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) is less effective and accompanied by more adverse effects than in younger patients. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) might improve the results, but increases the costs of treatment. We analyzed the costs of therapy and follow-up of patients with NHL treated with CHOP with or without G-CSF prophylaxis. DESIGN AND METHODS: Four hundred and eleven patients were randomized for treatment with CHOP or CHOP+G-CSF. A detailed study of treatment costs from randomization until 3 years of follow-up or death was performed in a subset of 100 out of 389 eligible patients. Because costs during follow-up were independent of the use of G-CSF during treatment, costs of follow-up and second-line treatment were calculated irrespective of the treatment arm. RESULTS: Total hospital costs for first-line treatment were 12178 [95% CI 10297 - 14059] for CHOP alone and 18356 [95% CI 15807 - 20906] for CHOP + G-CSF. Costs during follow-up showed a wide difference (range 74 - 53925) depending on disease status and choice of treatment in the case of relapse or progression. INTERPRETATION AND CONCLUSIONS: The clinical study showed no difference between the treatment arms in response, overall survival or event-free survival, while the costs were significantly higher in the G-CSF arm. We conclude that the addition of prophylactic G-CSF to CHOP chemotherapy is not cost-effective in these patients.

Aged↗
PubMed2004

In vivo induction of T-cell hyporesponsiveness and alteration of immunological cells of bone marrow grafts using granulocyte colony-stimulating factor.

BACKGROUND AND OBJECTIVES: Granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) transplantation is associated with a low incidence of graft-versus-host disease (GVHD) and has been used successfully in patients with human leukocyte antigen (HLA) matched/mismatched donors. This study evaluated the function of T cells and the quantities of immunological cells of G-BM. DESIGN AND METHODS: Bone marrow was obtained from fifteen donors by aspiration. Lymphocyte proliferation ability, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) secreted by T cells were determined using a monotetrazolium (MTT) assay and sandwich enzyme-linked immunosorbent assay (ELISA), respectively. T-cell subgroups, dendritic cell (DC) subsets, CD4(+)CD25(+) regulatory T cells and the expression of CD28/CD80/CD86 molecules on monocytes, B and T cells were analyzed using flow cytometry. RESULTS: G-CSF treatment decreased the quantities of IFN-gamma secretion dramatically (p=0.007) and IL-4 moderately (p=0.027), leading to higher ratios of IL-4/IFN-gamma (p=0.004). We confirmed T-cell hyporesponsiveness and lower expression of CD28/CD80/CD86 on monocytes, B and T cells. The absolute values of lymphocytes, T cell subgroups, CD3+CD4-CD8- cells, CD8+CD28- cells and B cells in bone marrow grafts were similar before and after G-CSF treatment. The number of monocytes per microliter was increased 2.13-fold, while the numbers of CD4(+)CD25(+) regulatory T cells were unchanged. DC2 were preferentially increased. INTERPRETATION AND CONCLUSIONS: Our results suggest that bone marrow T-cell hyporesponsiveness could be induced and that the increase of monocytes and DC2 and the downregulation of CD28/CD80/CD86 co-stimulatory signals were produced by in vivo use of G-CSF; this may be related to the preferential increase of monocytes and DC2 and the downregulation of CD28/CD80/CD86 co-stimulatory signals.

Adolescent↗
PubMed2004

Basal CD34(+) cell count predicts peripheral blood progenitor cell mobilization and collection in healthy donors after administration of granulocyte colony-stimulating factor.

We analyzed factors predicting CD34(+) cell mobilization and collection after granulocyte colony-stimulating factor (G-CSF) administration in 47 healthy donors. Basal CD34(+) cell count and sex were the two variables that significantly predicted a better CD34(+) cell mobilization, and greater age was the only variable associated with lower CD34+ cell yields.

Adolescent↗
PubMed2005

Phase II study of a single pegfilgrastim injection as an adjunct to chemotherapy to mobilize stem cells into the peripheral blood of pretreated lymphoma patients.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of pegfilgrastim, in combination with salvage chemotherapy, in mobilizing CD34(+) stem cells into the peripheral blood of pretreated lymphoma patients. DESIGN AND METHODS: This was an open-label phase II study including 25 pretreated patients (Hodgkin's disease=4; aggressive non-Hodgkin's lymphoma=21). The primary end-point of the study was the successful mobilization of a target cell dose of 2x10(6) CD34(+) cells/kg in lymphoma patients receiving ifosfamide, epirubicin and etoposide (IEV) chemotherapy and a fixed dose (6 mg) of pegfilgrastim given as single subcutaneous injection. RESULTS: Following chemotherapy, all patients had grade 4 neutropenia that lasted a median of 1.5 days (1-3). Pegfilgrastim treatment was well tolerated and only 2/25 patients required pain-control medication. CD34+ cells were mobilized in all patients. The median (range) peak value of peripheral blood CD34+ cells after IEV chemotherapy and pegfilgrastim was 141x10(6)/L (12.8-386) and occurred almost invariably on day +14 (13-16). Twenty-three of the 25 patients underwent a single standard volume leukapheresis to collect a median of 8.7x10(6) CD34(+) cells/kg (1.78-17.3). Twenty four/25 patients (96%) reached the target cell dose of 2x10(6) CD34(+) cells/kg. High concentrations of circulating CD34+ cells (> 50x10(6)/L) were observed for several days after the achievement of the peak value. All the study patients were transplanted with their pegfilgrastim-mobilized CD34(+) cells and showed a rapid and sustained engraftment after high-dose chemotherapy. INTERPRETATION AND CONCLUSIONS: Our results show that pegfilgrastim as an adjunct to chemotherapy is a predictable and highly effective mobilization regimen in pretreated lymphoma patients.

Adult↗