Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3'-azido-3'-deoxythymidine (AZT), the main antiviral drug used in AIDS treatment, is known to induce anemia and neutropenia. These effects have been attributed to its toxicity to hematopoietic progenitors. In this report, we present a new approach to reduce AZT hematotoxicity by using an inhibitory factor of the hematopoietic stem cells, the tetrapeptide AcSerAspLysPro (AcSDKP, Seraspenide), which has been shown to increase the survival of mice subjected to high doses of chemotherapy and to block reversibly the cycling of human granulocyte-macrophage colony forming unit (CFU-GM) and burst forming unit erythroid (BFU-E) progenitors. Normal bone marrow mononuclear cells (BMMNC) from 14 subjects were incubated with or without AcSDKP (10(-10) M) for 20 h and with or without AZT (100 microM) for another 2 h. After washing, cells were plated in methylcellulose in the presence of interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin (EPO). Under these conditions, the preincubation of cells with AcSDKP reduced significantly the toxicity of AZT to both BFU-E and CFU-GM at least in 3 out of 8 and 4 out of 10 cases, respectively. A careful statistical analysis of these observations indicates that AcSDKP may be an efficient factor in preserving progenitors against AZT-induced hematopoietic toxicity.
 ...
PMID:The tetrapeptide AcSerAspLysPro (Seraspenide), a hematopoietic inhibitor, may reduce the in vitro toxicity of 3'-azido-3'-deoxythymidine to human hematopoietic progenitors. 824 56

This report describes a patient with combined immune deficiency associated with congenital neutropenia (CID/CN) and reports a partial characterization of his hematopoietic abnormalities. The CID/CN syndrome described is characterized by neutropenia and by deficiencies in B-lymphoid and T-lymphoid cell number and function. Red cell and platelet counts were normal. In vitro assays indicate that the myeloid lineage was developmentally arrested at the level of the committed monocyte/granulocyte progenitor (CFU-GM), while precursors to the CFU-GM progenitor were normal. In vitro studies showed that the defect in myeloid development was not corrected with G-CSF or GM-CSF. However, combinations of cytokines present in conditioned media from the T-cell lines MO or C5MJ, or defined multiple cytokine combinations containing IL-1, IL-3, GM-CSF, kit ligand, IL-6, and IL-9, restored myelopoiesis in-vitro. In contrast, C5MJ-conditioned media did not correct deficiencies in immune function in the patient's lymphocytes and accessory cells. No abnormalities in the production of G-CSF, GM-CSF, M-CSF, or IL-1 from the patient could be identified to account for the defects in myelopoiesis orimmune function.
 ...
PMID:Dyshematopoiesis in combined immune deficiency with congenital neutropenia. 825 11

Using a bioassay for hematopoietic progenitor cells we looked for mechanisms causing clozapine induced neutropenia and agranulocytosis. Micro-agar-cultures of normal peripheral blood mononuclear cells (MNC) of eight patients currently treated with clozapine and of eight probands not receiving any kind of pharmacological treatment were incubated with increasing concentrations of clozapine (0, 7.5, 15, 30 micrograms/ml). Erythropoiesis and megakaryopoiesis were totally unaffected by clozapine. A biologically relevant suppression of granulopoiesis (CFU-GM) could only be shown in cultures incubated with 30 micrograms/ml clozapine. Cytokine analysis presented a strictly dose-dependent suppression of GM-CSF and neopterin release in all cultures. There was no difference between patients and controls at any clozapine concentration. The data support a possible role for cytokines as one mediator of the agranulocytosis producing effects of clozapine.
 ...
PMID:Effects of clozapine on hematopoiesis and the cytokine system. 827 81

High dose methylprednisolone (HDMP) has been used in induction treatment and in leukopenia of acute leukemia. We report the case of a 14-year-old girl with acute myelomonocytic leukemia (AMML) who developed a pseudorelapse after receiving an oral HDMP trial (30 mg/kg/day PO in the morning for 15 days) to overcome neutropenia. She presented with severe bone pain at the end of treatment. Bone marrow examination revealed 53% young promyelocytes (some with a large nucleolus), 2% myeloblast, 5% monocyte, and increased cellularity. Bone pain and promyelocytes regressed spontaneously while maintenance treatment continues. We advise that a pseudorelapse must be borne in mind after HDMP and probably GM-CSF treatments in acute leukaemias.
 ...
PMID:Pseudorelapse in acute myelomonocytic leukemia after high dose methylprednisolone. 770 84

Substantial increases in dose-intensity of chemotherapy yield a severalfold increase in complete remission rates and durable responses in several types of malignant disease. Hematopoietic colony-stimulating factors decrease the duration of the resultant severe neutropenia but optimal dosing regimens of these cytokines have not yet been determined. This study was designed to explore the use of both yeast-derived and E. coli-derived GM-CSF given pre- and postchemotherapy with an intensive combination chemotherapy regimen. The chemotherapeutic regimen consisted of cyclophosphamide 5000 mg/m2, etoposide 1500 mg/m2, and cisplatin 150 mg/m2 (DICEP). Patients receiving either yeast-derived GM-CSF (6.5 days) or E. coli-derived GM-CSF (6.0 days) had a shorter duration of severe granulocytopenia with an absolute granulocyte count below 300/microL than patients receiving no GM-CSF (11.0 days, p = 0.0001). Administration of GM-CSF for 6 days immediately preceding DICEP did not further shorten the duration of cytopenia. E. coli-derived GM-CSF given at doses above 5 micrograms/kg was poorly tolerated and offered no hematologic advantage. Lower doses (3 micrograms/kg) of the E. coli product were better tolerated but still produced more toxicities than yeast-derived GM-CSF. The yeast-derived product produced no local skin reactions and decreased the incidence of nonhematologic and all grade 3 or 4 toxicities compared to the control group.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor given before dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). 829 69

The clinical benefits of the haematopoietic growth factors (HGFs) granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in conjunction with bone marrow transplantation (BMT) have been established from numerous phase II/III clinical trials. Trials with filgrastim (recombinant G-CSF) have shown that it reduces the period of severe neutropenia by about one week, which leads to a reduction in infectious complications and earlier discharge from hospital. Similar clinical effects have been shown in placebo-controlled trials with recombinant GM-CSF. The effect of other HGFs on haematopoietic reconstitution has been investigated in animals and preliminary human studies, however, further data are required before their clinical efficacy can be determined. G-CSF is well tolerated in the BMT setting. GM-CSF also appears to be well tolerated at low doses, but increased toxicity may be seen at higher dosages. Clinical studies have also indicated that the HGFs do not stimulate the proliferation of leukaemic cells, furthermore, graft-versus-host disease (GVHD) is not enhanced by the use of growth factors. Pharmacological purging of the bone marrow may lead to a reduction in the granulocyte-macrophage colony-forming unit (CFU-GM) content of transplanted marrow. An alternative purging approach is the positive selection of CD34+ marrow stem cells. This technique may also be used to select stem cells from the peripheral blood for use in conjunction with or as an alternative to autologous or allogeneic BMT.
 ...
PMID:A review of the efficacy and tolerability of recombinant haematopoietic growth factors in bone marrow transplantation. 833 33

Bone marrow transplantation (BMT) is a rescue therapy used in conjunction with high-dose chemotherapy, which is an effective treatment for overcoming resistant disease in selected malignancies. However, highly intensive preparative regimens produce severe life-threatening toxicity which may be haematological or non-haematological. Despite extensive supportive care including isolation, empiric antibiotic use and parenteral nutrition, toxicity is associated with a significant level of morbidity and mortality. A major cause of morbidity is infection resulting from the period of neutropenia caused by the ablation of the patient's marrow. The haematopoietic growth factors (HGFs) may provide effective therapy for improving haematopoietic reconstitution and therapy decrease the risk of infection, days of hospitalisation and subsequently reducing overall treatment cost. They may also be useful for enhancing neutrophil function, improving bone marrow yield and mobilising peripheral blood progenitor cells (PBPC). Recombinant G-CSF or GM-CSF may, therefore, improve the safety of the BMT procedure and increase its application to a greater number of patients.
 ...
PMID:The clinical consequences of haematological and non-haematological toxicity following bone marrow transplantation and the possible impact of haematopoietic growth factors. 833 34

Use of growth factors to augment hematopoietic recovery after cytotoxic therapy is a useful method for dose intensification. We wanted to evaluate the clinical and cost-effectiveness of granulocyte-macrophage colony stimulating factor (GM-CSF; Leucomax) in patients undergoing autologous bone marrow transplantation (ABMT) for Hodgkin's disease. Twenty-four patients with Hodgkin's disease were treated with high-dose chemotherapy and ABMT. Patients were then randomized in a double-blind manner to receive GM-CSF intravenously (10 micrograms/kg) over 6 h or placebo until the absolute neutrophil count (ANC) was greater than 1000/mm3 for 3 days. The study medication was stopped after 30 days. Patients treated with GM-CSF (n = 12) had shorter periods of neutropenia (median duration of an ANC of less than 1000 cells/mm3, 16 versus 27 days on placebo; p = 0.23), shorter periods of platelet-transfusion dependency (median duration, 13.5 versus 21 days on placebo; p = 0.03), shorter hospitalizations (median hospital stay, 32 versus 40.5 days on placebo; p = 0.0004). Other clinical outcomes, such as frequency and severity of toxicities, development of pneumonia or infection, in-hospital death, and response rate were similar in the two groups. Actuarial long-term disease free survival was 58% for patients treated with GM-CSF and 50% for patients who received placebo after 38 months of follow up (p = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of granulocyte-macrophage colony stimulating factor (GM-CSF) after autologous bone marrow transplantation for Hodgkin's disease. 834 51

Authors report their first experiences with the application of granulocyte-macrophage colony stimulating factor in 12 pediatric cancer patients (14 cases). The drug was given in a 5 micrograms/kg single daily dose subcutaneously. Patients were divided into three main indication groups: 1. Severe neutropenia (white blood cell count < 1.0 G/l) and sepsis (6 patients); 2. Prolonged neutropenia (white blood cell count: 1.0-2.0 G/l) and delay in treatment (3 patients); 3. Dose-escalation of chemotherapy in therapy-resistant cases (4 patients). Authors report that in all cases a substantial raise in white blood cell count could be achieved after 5-6 days of granulocyte-macrophage colony stimulating factor treatment. No side effects were detected except of a moderate local pain at the site of the injection. Authors suggest that in the above described dose and way of administration granulocyte-macrophage colony stimulating factor can be an effective agent in the treatment of chemotherapy-induced neutropenia in paediatric oncology.
 ...
PMID:[First experience with the use of granulocyte-macrophage colony stimulating factor in pediatric oncology]. 835 Nov 31

Recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-SCF) is currently being tested in clinical trials for the treatment of acute myeloid leukemias with two main intentions: reduction of neutropenia and recruitment of leukemic blasts into cell cycle to enhance cytarabine (ara-C) mediated cytotoxicity. We report a case of a fatal spleen rupture in a patient with acute monocytic leukemia (AML M5b) who was treated according to a clinical phase I/II protocol with rh GM-CSF priming and standard induction chemotherapy TAD 9 (thioguanine/ara-C/daunorubicin). During treatment we observed rapidly rising peripheral blast counts and the development of an acute abdomen. Ultrasound examination revealed splenomegaly due to diffuse cellular infiltration and spleen rupture. The patient died 17 days later due to pneumonia and renewed spleen hemorrhage. Bone marrow progenitor assays before treatment showed exclusive growth of monocytoid blast cell colonies (CFU-L). Colony growth could be stimulated with rh GM-CSF and blocked dose-dependently by a monoclonal anti-GM-CSF antibody. CFU-L proliferation also increased after stimulation with rh interleukin-3 (rh IL-3) and supra-additively with rh granulocyte colony-stimulating factor (rh G-CSF) combined with rh GM-CSF. Furthermore, rh GM-CSF induced surface marker expression of CDw 65 and CD 11b on isolated CFU-L blasts. After short-term suspension culture, rh GM-CSF enhanced the expression of CD 29- and CD 11b-adhesion molecules on peripheral blast cells. In summary, this case represents a fatal spleen rupture occurring during rh GM-CSF priming and induction chemotherapy for acute monocytic leukemia. Although the etiology of this spleen rupture remains uncertain, in view of our data we suggest special caution, when further testing this therapy protocol in acute leukemias with monocytic subtype and high peripheral blast cell counts.
 ...
PMID:Fatal spleen rupture during induction chemotherapy with rh GM-CSF priming for acute monocytic leukemia. Clinical case report and in vitro studies. 845 Jun 76


<< Previous 1 2 3 4 5 6 7 8 9 10