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)

The hematologic manifestations of HIV infection and AIDS are common and may cause symptoms that are life-threatening and impair the quality of life of these patients. The most important of these manifestations are cytopenias. Anemia and neutropenia are generally caused by inadequate production because of suppression of the bone marrow by the HIV infection through abnormal cytokine expression and alteration of the bone marrow microenvironment. Thrombocytopenia is caused by immune-mediated destruction of the platelets, in addition to inadequate platelet production. The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. Other causes of cytopenia in these patients include adverse effects of drug therapy, the secondary effects of opportunistic infections or malignancies, or other preexisting or coexisting medical problems that may be prevalent in the HIV-infected population. Diagnosis of the mechanism and cause of the cytopenia may allow for specific management. Optimal management of the underlying HIV infection is essential, and mild cytopenia in asymptomatic patients may need no specific management. Supportive care for anemia includes the use of erythropoietin in addition to the judicious use of red blood cell transfusions. Therapy for neutropenia includes the use of the myeloid growth factors G-CSF and GM-CSF. Immune-mediated thrombocytopenia may be treated with a combination of zidovudine, corticosteroids, IVGG, and splenectomy. Platelet transfusions are sometimes needed for the treatment of thrombocytopenia caused by decreased production. Other hematologic manifestations such as hypergammaglobulinemia and lupus anticoagulants are commonly asymptomatic and usually require no specific therapy, but they can rarely cause morbidity and require specific interventions.
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PMID:Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. 909 37

This is a continuation of a HeCOG previous trial utilizing carboplatin and vindesine in conventional doses as a non-toxic regimen provided easily on an outpatient basis in NSCLC. In the present study we investigated whether an intensified dose-carboplatin could yield a better response. Carboplatin at a dose of 450 mg/m2 dose in combination with vindesine 3 mg/m2 every three weeks and GM-CSF support was used in a phase II study to treat 44 patients with non-small cell lung cancer (NSCLC). As compared to our previous study carboplatin dose intensity was increased from 75 mg/m2/wk to 150 mg/m2/wk. Six patients (13.6%) responded to treatment and all were partial responders. The median duration of response was 5 months (range 1.5-9 month). After a retrospective analysis a dose response effect was not evident at different carboplatin AUC doses. Twenty patients (45.45%) experienced thrombocytopenia and seventeen patients (38.6%) anemia as major toxicities. This study shows that in NSCLC a dose-response effect does not exist between carboplatin dose intensification and response rate cannot be traced.
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PMID:Intensified carboplatin regimen with GM-CSF support in non-small cell lung cancer (NSCLC). A Hellenic Co-operative Oncology Group Study (HeCOG). 914 68

The aim of this study was to evaluate tolerability and efficacy of Leucomax (Sandoz/Schering Plough) used for neutropenia in patients with small cell lung cancer (SCLC) treated with etoposide and cisplatin. The potential influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on chemotherapy relative dose intensity (RDI) was also evaluated. The chemotherapy used was the following, cisplatin 50 mg m-2 i.v. 1 and 7 day, etoposide 170 mg m-2 i.v. 3-5 days, q 3-4 weeks. Patients received a median of six cycles (range 2-8) over 4-36 weeks (median: 20). Thirty-two consecutive patients were treated, six were excluded. Eleven patients received GM-CSF 5 micrograms kg-1 s.c. due to absolute neutrophil count (ANC), 1000/mm3 until recovery (ANC > 2000 mm3) or during 7 days, and thereafter prophylactically 24 hours post subsequent chemotherapy cycles for 7 days. Four patients received single GM-CSF course during the terminal disease phase. In 11 patients, there was no neutropenia requiring GM-CSF during the whole treatment course. Toxicity of chemotherapy was high, including thrombocytopenia, neutropenia, anaemia, mucositis, fever and hypotension. GM-CSF toxicity was the following, first dose reaction-one patient, local erythema-two patients, arthralgia-one patient, hypotension, chills, fever requiring GM-CSF discontinuation one patient RDI of cisplatin/etoposide was 0.77/0.62 in GM-CSF group, and 0.90/ 0.80 in patients who didn't receive Leucomax. Overall objective response rate to chemotherapy and complete response rate were 80% (21/26), 26% (7/26) and median survival of all patients was 10 months. Median disease free survival was 8 months. Four patients are alive, two patients lost during progression, 20 died. Administration of GM-CSF did not appear to improve RDI of chemotherapy, overall response rate (RR) nor survival in this phase I/II clinical study. RDI of chemotherapy was reduced in patients receiving GM-CSF due to thrombocytopenia and/or extrahaematologic toxicity of chemotherapy.
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PMID:Tolerability and efficacy of GM-CSF [Leucomax] in patients with small cell lung cancer treated with intensive chemotherapy. 915 70

In myelodysplastic syndromes (MDS), pancytopenia and defective function of neutrophils and platelets lead to a high risk of infectious and hemorrhagic complications. The progression to acute myeloid leukemia adds to morbidity and mortality. Supportive care including red blood cell and platelet transfusions are still the cornerstone of therapeutic management. However, the clinical use of the recombinant hematopoietic growth factors has enlarged the range of therapeutic applications in patients with MDS. It is possible to reverse neutropenia in MDS patients by administration of G-CSF (granulocyte colony stimulating factor) or GM-CSF (granulocyte-monocyte colony stimulating factor). Because of the lower incidence of adverse events, G-CSF is preferable. However, neither G-CSF nor GM-CSF have been shown to reduce the rate of severe infection or mortality from infection when given prophylactically. In the case of a severe infection, therapeutic administration of G-CSF together with antibiotics might be justified in otherwise neutropenic MDS patients. Preliminary data suggest it to be possible to identify MDS patients with a higher than 50% chance of reversal of anemia or transfusion dependency by treatment with high-dose erythropoietin (EPO). Since patients with only slight impairment of erythropoiesis and no transfusion dependency have the highest response rates but need EPO the least, pharmacoeconomic analyses are urgently needed. Controlled randomized trials will have to ascertain whether combinations of EPO with G-CSF or GM-CSF are of benefit. Clinical studies with thrombopoietin (megakaryocyte growth and differentiation factor) have to be initiated to find out whether thrombocytopenia in MDS can be reversed.
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PMID:Clinical use of hematopoietic growth factors in patients with myelodysplastic syndromes. 919 74

Neoadjuvant chemotherapy is used to improve patients' survival in locally-advanced and inflammatory breast cancer and to increase conservative surgical procedures in bulky tumours. Pathological complete responses are unusual. The aim of this pilot study was to assess the clinical and pathological response rates and to evaluate toxicity with a new protocol of primary chemotherapy in 50 high-risk breast cancer patients. All tumours were > 3 cm and had at least one other adverse prognostic factor: lymph node involvement (32 N1, 6 N2), SBR grade III (20), aneuploidy (29), negative hormonal receptors (19). Patients were treated by 3-week cycles of THP-doxorubicin 20 mg/m2 D1 to 3, vinorelbine 25 mg/m2 D1 and 4, cyclophosphamide 300 mg/m2 and 5-fluorouracil 400 mg/m2 D1 to 4 (TNCF). 38 patients received G-CSF or GM-CSF support. After 4-6 cycles, all underwent surgery (39 conservative, 11 modified radical). Tumour response was assessed clinically, by mammography and echography and on pathological specimens. An objective clinical response was observed for 43 patients: 26 complete (51%) and 18 partial (37%). After pathological review, 11 patients (22%) were devoid of any tumour cells, 4 others (8%) had only in situ carcinoma. From 253 evaluated cycles, grade III-IV toxicity occurred, 81% with neutropenia, 25% with anaemia, and 20% with thrombocytopenia. All patients recovered. This regimen induced a severe but not life-threatening haematological toxicity and resulted in a high pathological response rate (30%).
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PMID:Clinical and pathological response to primary chemotherapy in operable breast cancer. 929 6

Haematopoietic growth factors are glycosylated proteins involved in the differentiation of pluripotent stem cells into committed progenitor cells, which eventually give rise to distinct haematopoietic cell lineages. Three recombinant hematopoietic growth factors--G-CSF, GM-CSF and erythropoietin--are currently commercially available for clinical use. G-CSF and GM-CSF are lineage-specific growth factor that regulate the production and function of granulocytic and monocytic cells. They have been shown to reduce the incidence of febrile neutropenia. Primary prophylactic administration is reserved for patients in which the expected incidence of febrile neutropenia is greater than 40% without haematopoietic growth factor. After a documented occurrence of febrile neutropenia in an earlier cycle, the secondary prophylactic administration of G-CSF or GM-CSF may be considered. However, in the absence of clinical data supporting maintenance of chemotherapy dose-intensity, dose reduction should be considered as an alternative to the use of haematopoietic growth factors. G-CSF and GM-CSF also shorten the period of neutropenia in patients undergoing high-dose chemotherapy with autologous bone marrow support. Erythropoietin is currently approved for treatment of anemia associated with cisplatin-based chemotherapy with the aim to reduce transfusion requirements.
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PMID:[Haematopoietic growth factors and solid tumors]. 936 42

The authors analyze the role of G-CSF and GM-CSF in hematological malignancies. These allow correction of drug-induced neutropenias and perhaps more importantly allow the increase of doses of chemotherapy to improve the antitumor effect, and permit the maintenance of full chemotherapy doses in elderly patients. They can also mobilize peripheral blood stem cells for autologous and recent allogeneic transplantation. They can be useful at low doses in correcting the spontaneous neutropenia of bone marrow failures. A specific antitumor effect, on the other hand, is extremely hypothetical. Erythropoietin by contrast has been disappointing in the treatment of anemia in spontaneous bone marrow failures. For the treatment of thrombocytopenias, preliminary results with thrombopoietin are encouraging. Combinations of growth factors will probably improve results obtained with one factor. However, in all cases the cost/benefit of growth factors will have to be strictly established.
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PMID:[Hematopoietic growth factors in the treatment of malignant hemopathies]. 936 44

A hemoglobin F (HbF) level between eight and nine percent divides sickle cell anemia (SS) patients into two populations, according to the kinetics of circulating burst forming units-erythroid (BFU-E), long term culture-initialing cells (LTC-IC), and cytokine plasma concentrations. The SS patients with HbF levels lower than 8-9% are more anemic (LFSS patients) than those with HbF levels higher than 8-9% who have less severe anemia (HFSS patients). We report here that the level of erythropoiesis [evaluated by the levels of soluble transferin receptors (sTfR)] is not identical in these two patient populations, supporting the idea that a different set of regulatory mechanisms might be required to maintain the two levels of increased hematopoiesis. The plasma sTfR concentration was increased in all SS samples compared with controls (P < 0.002) and sTfR levels were negatively correlated with peripheral HbF%. (r = -0.574, P < 0.002). Furthermore, sTfR levels were higher in LFSS than in HFSS patients. Erythropoietin (Epo) levels were increased in the plasma of LFSS individuals (range = 34-215 ml U/ml), while the values in HFSS patients were in the normal range (3-20 ml U/ml). Furthermore, we identify here stem cell factor (SCF) and transforming growth factor-beta (TGF-beta) as regulatory factors specifically affected by the presence of SS genotype and its level of severity. The plasma concentrations of SCF and TGF-beta were increased compared with normal controls and high levels of SCF (up to 7,000 pg/ml) were detected in LFSS patients. The latter also showed increased proportion of SCF+ CD34 enriched circulating cells (49%). Low SCF in HFSS patients is associated with elevated TGF-beta, suggesting a regulatory role of the latter on either SCF release or c-kit expression in progenitor cells. Occasional elevation of granulocyte macrophage-colony stimulating factor (G-CSF), interleukin (IL)-7, and macrophage inflammatory protein (MIP)-1alpha in plasma of SS patients is not specific because no relation to HbF could be demonstrated. All plasma tested for leukemia inhibitory factor (LIF) were negative. Data presented here, complementing previously published information, supports a model in which HFSS patients achieve a balance between inhibitory (TGF-beta) and stimulatory (SCF, IL-3) factors, resulting in moderate erythropoietic response. In contrast, in LFSS patients, low levels of TGF-beta and the increased release of GM-CSF and SCF maintain the intense erythropoiesis in response to higher erythropoietic stress, in these more severe patients.
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PMID:Circulating cytokines response and the level of erythropoiesis in sickle cell anemia. 992 1

The aim of this prospective study was to determine whether treatment with a combination of GM-CSF and erythropoietin (rhEpo) can improve the anemia associated with low risk myelodysplastic syndrome (MDS), namely refractory anemia (RA), RA with ring sideroblasts (RAS), and RA with excess of blasts (RAEB) with bone marrow blasts less than 10%. Eligibility criteria included an Hb level of less than 10.5 g/dl for newly diagnosed patients, or symptomatic anemia. GM-CSF was given at a dose of 3 microg/kg s.c. on days 1-2, rhEpo at a dose of 60 U/kg s.c. on days 3-5. No treatment was given on days 6-7. Patients were followed-up with full blood count on a weekly basis. The treatment was repeated for a total of 6 weeks. At that time, if a rise in Hb above 1.5 g/dl had not been achieved, the dose of rhEpo increased to 120 U/kg. Post-treatment evaluation was performed at the completion of 12 weeks. Erythroid response was defined as good (GR), if an increase in untransfused Hb values above 2 g/dl or a 100% decrease in red blood cell transfusion requirements, over the treatment period was observed, while an increase in untransfused Hb values 1-2 g/dl or a >50% decrease in transfusion requirements, were considered as partial response. Responders continued to receive the same treatment until disease progression. Nineteen patients (13 male and six female) with a median age of 69 years were enrolled in the study. The FAB subtypes were: RA one case, RAS eight cases and RAEB 10 cases. Ten of 19 patients (52.6%) responded to the treatment: 7/19 (36.8%) achieved a GR and 3/19 (15.8%) a PR. Six of eight (75%) patients with RAS, one case with RA and 3/10 (30%) of cases with RAEB responded to treatment. Pretreatment serum epo levels were generally low (less than 200 Mu/ml) in responding patients. At the completion of the initial 12 weeks, 8/12 responding patients (5 RAS, 2 RAEB and 1 RA) continued to receive the same treatment. All responding patients with RAS continued to show an erythroid response in a time period from 3 to 24 months, whilst one patient with RA and two with RAEB did not have a continuing response at 2, 4 and 12 months, respectively. The above data suggest that the combination of rhEpo and GM-CSF should be recommended in all cases with RARS. However, the clear indication of this combination for other patients with MDS remains to be determined.
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PMID:Treatment of anemia in low risk myelodysplastic syndromes with granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin. 1040 Apr 15

To increase the dose-intensity of two drugs in metastatic breast cancer, we tested the feasibility, in phase I studies, of two schedules of epirubicin (E) and cyclophosphamide (C) - sequential (E--> C) and alternating (E/C) - with respect to the standard combination (EC). Drugs were given at three planned-dose levels, plus either G-CSF or GM-CSF. Patients with metastatic (30), inoperable stage IIIb (2) or inflammatory (7) breast cancer were treated. The doses of EC, given every 21 days (4 cycles), were 75/1500, 82.5/2250, 90/3000 mg/m2. In the E/C schedule, epirubicin was given at cycles 1, 3 and 5, and cyclophosphamide at cycles 2, 4 and 6. In the E--> C schedule, three cycles of epirubicin then three cycles of cyclophosphamide were administered. In both experimental schedules, drugs were given every 14 days for 6 cycles at doses of 100, 110, 120 mg/m2 (E) and 2000, 3000, 4000 mg/m2 (C). The average relative dose-intensity was 1.2-fold and 2-fold greater with E/C and E--> C, respectively, than with EC. The third level dose was feasible with all schedules. Grade 4 leucopenia occurred in 77% of patients. Thrombocytopenia was absent in 6 cases and grade 4 in 12 (30.8%). Eighty-one percent of patients on experimental schedules required red blood cell support versus 44.4% of patients on EC. At the third level, platelet transfusions were more frequent among patients treated with EC (27. 8%). Non-haematological toxicity was mild: about 20% of patients experienced grade 3 vomiting, irrespective of schedule. Only 2 patients had grade 3 mucositis; no patient developed heart failure. Fever (61% of patients) and bone pain (55.5% of patients) were relevant in the GM-CSF treated groups and 12 patients shifted to G-CSF. The overall response rate was 84.6%: 5/39 (12.8%) complete response and 28/39 (71.8%) partial response. At 30/9/98, median survival was 29.5 months, with no difference between patients with metastatic and stage IIIb/inflammatory breast cancer. Median follow-up of surviving patients was 62 months (range 17-83). The 5-year estimated survival was 19% (95% confidence intervals = 7-31%). Rapidly alternating or sequential cycles of epirubicin and cyclophosphamide with CSF support is a feasible strategy that allows a higher increase of dose-intensity of the single drugs. Hospitalization and anemia were more frequent with the experimental schedules, and thrombocytopenia with the standard schedule. Overall, this intensified therapy was very active.
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PMID:The impact of schedule on acute toxicity and dose-intensity of high-dose chemotherapy with epirubicin and cyclophosphamide plus colony stimulating factors in advanced breast cancer. 1040 45


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