Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase II trial of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin included 54 chemotherapy-naive patients with advanced non-small cell lung cancer. Eligibility mandated Eastern Cooperative Oncology Group performance status of 0 or 1 and adequate hematologic, renal, and hepatic function. Paclitaxel 135 mg/m2 over 24 hours preceded carboplatin dosed to an area under the concentration-time curve of 7.5. Six planned courses were given every 3 weeks. Granulocyte colony-stimulating factor was introduced during the second and subsequent cycles, and paclitaxel increased 40 mg/m2/cycle (maximum, 215 mg/m2) in patients with absolute neutrophil and platelet nadirs exceeding 500/microL and 50,000/microL, respectively. Grade 3 or 4 neutropenia, observed in 54% of patients during cycle 1, declined to 35% during cycle 2 and to 22% or less during cycles 3 through 6. Neuropathy, myalgias/arthralgias, and thrombocytopenia were mild but cumulative. In 53 evaluable patients, the objective response rate was 62%, with 9% complete remissions and a median response duration of 6 months (range, 1 to 19+ months). At median potential follow-up of 16 months, 9% of patients remain progression free (52+ to 80+ weeks). Median survival is 12.5 months; 1-year survival is 54%. Paclitaxel/carboplatin is highly active in advanced non-small cell lung cancer; granulocyte colony-stimulating factor abrogates neutropenia as the dose-limiting toxicity, but has no effect on the cumulative incidence of thrombocytopenia or treatment delays. One-hour paclitaxel infusion is minimally myelosuppressive, logistically easier, and less costly. A follow-up study combined paclitaxel (175 mg/m2) over 1 hour followed by carboplatin (area under the concentration-time curve, 7.5). In the absence of grade 4 myelosuppression, paclitaxel was increased 35 mg/m2/cycle (maximum, 280 mg/m2). Granulocyte colony-stimulating factor was implemented only after neutropenic fever or grade 4 neutropenia. Of 17 patients entered, 13 are evaluable for toxicity and seven for response. Four patients have sustained a partial response, two a minor response, and one stable disease. The incidence of grade 3 or 4 neutropenia, thrombocytopenia, and anemia in cycle 1 was 38%, 16%, and 0%, respectively, and 72%, 28%, and 28%, respectively, during cycle 2. Major nonhematologic toxicities include myalgias and arthralgias (54%) and fatigue and neuropathy (78%), the latter cumulative and progressive over successive cycles. Preliminary data suggest comparable activity for the 1- and 24 hour paclitaxel infusions in combination with carboplatin. The more severe neuropathy of the 1-hour paclitaxel/carboplatin combination may be related to the paclitaxel dosing schema (175 mg/m2 to as high as 280 mg/m2).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Paclitaxel by 24- or 1-hour infusion n combination with carboplatin in advanced non-small cell lung cancer: the Fox Chase Cancer Center experience. 754 25

Cytokines are a class of signal peptides which represent a major communication network in living organism. Over the last decade, the discovery, cloning and purification of hematopoietic cytokines (interleukins, hematopoietic growth factors) has increased our understanding of the regulation, proliferation, differentiation and function of hematopoietic cells. More recently, the large scale production of the recombinant forms of these molecules has enabled to treat the patients with pharmacologic doses of cytokines. The therapeutic activity of interferon-alpha (IFN-alpha) has been demonstrated in patients with chronic myeloid leukaemia and other chronic myeloproliferative syndromes. IFN-gamma is useful in the prevention of infections in patients with chronic granulomatous disease. Erythropoietin (EPO) was the first hematopoietic growth factor available for clinical use, initially to treat anaemia in renal failure patients. The next cytokines introduced into the clinic were granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF). They are used successfully in haematological malignant disorders to stimulate granulopoiesis after chemotherapy or bone marrow transplantation and to help mobilise marrow stem cells for peripheral blood stem cell transplantation. Interleukin (IL)-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. However, the value of these agents remains to be established.
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PMID:[Cytokines in the treatment of blood diseases]. 754 26

Sixty-four consecutive patients with locally advanced (n = 7) or metastatic breast cancer (n = 57), were treated with a combination of laevofolinic acid 100 mg m-2 plus 5-fluorouracil 340 mg m-2 i.v. on days 1-3, cyclophosphamide 600 mg m-2 i.v. on day 1 and epirubicin 90 mg m-2 i.v. on day 1. Epirubicin dose was progressively escalated by 10 mg m-2 per cycle up to 120 mg m-2 in the absence of dose-limiting toxicities. Granulocyte colony-stimulating factor (G-CSF) was given subcutaneously in order to prevent neutropenia. Epirubicin dosage could be increased to 100 mg m-2 in 53 patients (87%), to 110 mg m-2 in 31 patients (51%) and to 120 mg m-2 in 18 cases (30%). In most patients the dose-limiting toxicity was represented by myelosuppression. A statistically significant correlation was found between median white blood count (WBC) or absolute neutrophil count (ANC) nadir and epirubicin dose level (P = 0.009; P = 0.008). Moreover, a statistically significant correlation was observed between the number of chemotherapeutic cycles, nadir ANC and WBC and the occurrence of anaemia and thrombocytopenia of increasing severity. These data suggest the occurrence of progressive cumulative bone marrow toxicity. Although patients who reached different epirubicin levels showed differences in mean dose intensity, such differences were not statistically significant. No correlation was found between the increase in dose intensity and type, rate or duration of objective responses. In patients with metastatic breast cancer the overall response rate was 72% (95% CL 66-78%) with a 25% complete response rate. Median duration of response was 10 and 13 months respectively for complete and partial responses. All patients with locally advanced breast cancer had an objective response and underwent radical mastectomy. Projected median survival of the whole series of patients with metastatic breast cancer was 20 + months. These data demonstrate that the combination of 5-fluorouracil with laevofolinic acid, cyclophosphamide and epirubicin is very active against metastatic breast cancer. Use of G-CSF allows epirubicin dosage to be increased up to 120 mg m-2 cycle-1, but its use may be linked to the occurrence of sometimes severe cumulative haematological toxicity.
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PMID:Laevofolinic acid, 5-fluorouracil, cyclophosphamide and escalating doses of epirubicin with granulocyte colony-stimulating factor support in locally advanced and/or metastatic breast carcinoma: a phase I-II study of the Southern Italy Oncology Group (GOIM). 757 76

Monosomy 7 (Mo7) and leukaemia predisposition are associated with Kostmann's disease (KD). The recent introduction of long-term recombinant HuG-CSF treatment in patients with KD, whilst showing significant reductions in infectious complications and improved quality of life, might also be associated with an increased risk of developing karyotypic abnormalities, myelodysplasia (MDS) and acute myeloid leukaemia (AML). We describe a case of an identical twin with probable autosomal dominant KD who developed anaemia, Mo7/MDS and AML at 18, 30 and 50 months respectively from starting r-metHuG-CSF (filgrastim) treatment. Further patient analyses are required to establish the natural history of KD and to determine what role, if any, filgrastim plays in altering the pathobiology of this disorder.
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PMID:Kostmann's disease, recombinant HuG-CSF, monosomy 7 and MDS/AML. 757 23

This study assessed the clonality of hypoplastic and subsequent recovery phases before the development of overt leukemia by molecular genetic analysis. We describe a boy who had transient granulocytopenia and anemia before the development of acute lymphoblastic leukemia (ALL). Initially, his bone marrow was hypocellular with 23.6% of lymphoblastic cells, whereas subsequent marrow after the administration of granulocyte colony-stimulating factor (G-CSF) appeared almost normal without any lymphoblasts. At diagnosis, we found the rearrangement of T cell receptor (TCR) delta gene in the leukemic cell DNA by Southern blot hybridization. The junctional sequence of the V delta 2-D delta 3 recombination of leukemic cells obtained by polymerase chain reaction (PCR) was used for a clonospecific probe. Using the probe, the presence of leukemic clone in the materials before and after diagnosis was examined. We found that the clonospecific probe could detect one leukemic cell in 10,000 normal cells, and we demonstrated the presence of the leukemic clone at the initial hypoplastic and the subsequent recovery phase. The PCR method is very useful to confirm the presence of leukemic clone even in a retrospective analysis using low-quality materials and may be helpful to understand the pathogenesis of a smoldering preleukemic phase.
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PMID:Detection of neoplastic clone in the hypoplastic and recovery phases preceding acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain gene. 762 Sep 27

The pathophysiological abnormalities leading to marrow failure and leukemogenesis in children with Fanconi anemia (FA) are not understood. We tested the hypothesis that the Fanconi anemia mutation results in insufficient production of hematopoietic growth factors by stromal cells by quantifying constitutive and induced production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and steel factor (SF) by untransformed fibroblasts from eight patients with FA from five different families. While no abnormalities were noted in SF or M-CSF production, we noted substantial variability in IL-6, GM-CSF, and G-CSF responses of cells obtained from different FA patients. Responses ranged from blunting to augmentation when compared to normal controls. Because there was variation between fibroblast strains from affected members of two multiplex sibships, however, it is clear that neither augmentation nor blunting is a direct effect of the FA mutations. In addition, because there was discordance between the G-CSF responses and the GM-CSF and IL-6 responses, the abnormalities noted in IL-1 responsiveness must lie distal to IL-1 receptor function and to stimulus-response coupling pathways shared between the three cytokines.
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PMID:Constitutive and induced expression of hematopoietic growth factor genes by fibroblasts from children with Fanconi anemia. 769 32

Erythropoietin, alone or in combination with colony-stimulating factors, is a promising agent in the treatment of patients with cancer-related 'anemia of chronic disorders', chemo/radiotherapy-induced anemia, or anemia due to myelodysplastic or myeloproliferative syndromes. In the first two groups, at least half of the patients can be expected to respond to erythropoietin alone, with an average response delay of about 4 weeks and maximal responses at weekly doses of approximately 1000 U/kg. In myelodysplastic syndromes, only 10-20% of patients respond to conventional doses of erythropoietin, but doses exceeding 1000 U/kg weekly in combination with granulocyte colony-stimulating factor yield response rates of about 40%. Although these results show that hematopoietic growth factors can be used successfully to treat cancer-related anemias, economic constraints preclude their use at the present time.
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PMID:Hematopoietic growth factors and the treatment of tumor-associated anemias. 794 10

Reverse transcriptase-polymerase chain reaction showed that interleukin 3, IL-4, IL-5, IL-6, interferon-gamma and stem cell factor mRNA expression were higher in 15-deoxyspergualin-treated spleen cells than in control spleen cells. Increased IL-2 and IFN-gamma mRNA expression were observed in 15-deoxyspergualin-treated bone marrow cells. On the other hand, increased platelet counts in BALB/c-->C3H/He bone marrow chimeras were observed from days 20 to 33 in our previous work, when they were treated with 15-deoxyspergualin from days 14 to 25. In contrast, marked leukocytopenia and anemia were simultaneously observed, although a marked leukocytosis and a rapid recovery of anemia were observed on day 33 and thereafter. To analyze effects of 15-deoxyspergualin on hematopoiesis and the immune system, we examined mRNA expression in bone marrow and spleen cells from BALB/c-->C3H/He bone marrow chimeras treated with 15-deoxyspergualin from days 14 to 25. Reverse transcriptase-polymerase chain reaction showed that IL-3, IL-4, IL-6, stem cell factor, granulocyte colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor mRNA expression were higher in 15-deoxyspergualin-treated chimeras than in control chimeras, indicating that these cytokines are responsible for an enhancement of hematopoiesis. It was conceivable that IL-6 supported thrombopoiesis in concert with other cytokines. On the contrary, increased IFN-gamma, IL-2, IL-3, IL-4, and IL-10 mRNA expression may play an immunosuppressive role in vivo.
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PMID:Effects of 15-deoxyspergualin in vitro and in vivo on cytokine gene expression. 797 17

In recent years, biologic response modifiers, including recombinant cytokines and hematopoietic growth factors, have been used to treat patients with refractory hematologic malignancies and solid tumors, as well as chemotherapy-associated myelosuppression and thrombocytopenia and treatment- and/or malignancy-related anemia. Various cytokines appear to be effective in patients with hematologic malignancies, but long-term and durable responses in the salvage setting are rare. In patients with solid tumors, such as renal cell carcinoma, malignant melanoma, and colorectal cancer, cytokines may have a limited role in primary therapy but are of little value in salvage therapy. Complications of malignancy and antineoplastic therapy are widely treated with hematopoietic growth factors, like granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, and more recently the interferons and interleukins have demonstrated a potential role in this setting.
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PMID:Biologic therapy in patients receiving salvage treatment. 809 Dec 47

Serum levels of erythropoietin and five other cytokines potentially operational in erythropoiesis were determined in patients with anemia of chronic disease. No correlation between erythropoietin levels and severity of anemia was found. A spectrum of abnormality was encountered among patients in whom there was less than expected erythropoietin response to increased levels of erythropoietin and among others in whom the erythropoietin levels were subnormal for their degree of anemia. Increased serum levels of interleukin-3, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were encountered in limited numbers of patients, especially those with increased erythropoietin levels. Deficient erythropoietin production is concluded to be the major cause of anemia of chronic disease.
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PMID:Serum levels of erythropoietin and selected other cytokines in patients with anemia of chronic disease. 813 91


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