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

Twenty patients with aplastic anemia underwent long-term administration (10 weeks) of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses from 50 to 800 micrograms/m2 per day by intravenous infusion or 50 to 100 micrograms/m2 per day by subcutaneous injection and re-combinant human erythropoietin (rhEPO) in doses ranging from 2000 to 8000 IU/m2 per day by intravenous injection three times a week for at least 4 weeks. The goal was to evaluate whether therapy ameliorated pancytopenia in these patients as well as to determine its safety. All assessable patients showed a substantial increase in absolute neutrophil count, with a recovery of myeloid components (granulocyte series) in the bone marrow, after 2 to 10 weeks of treatment. An increase > 1.5 g/dL in hemoglobin (Hb) concentration was observed in 2 patients (10%). A decrease > 50% in red cell transfusion requirement was observed in 2 patients (10%). Seven patients showed recovery of neutropenia, anemia, and platelet count. In addition, there was no serious infection before or during therapy, and side effects were mild. Of the 20 patients, 3 showed a dramatic improvement in severe anemia after 10 weeks of treatment accompanying a recovery of erythroid components in the bone marrow. They no longer require red cell transfusions and have had normal Hb concentrations and normal ferrokinetics. These results indicate that long-term administration of rhG-CSF and rhEPO may benefit some patients with aplastic anemia. Further studies will be necessary to elucidate the mechanism by which rhGCSF and rhEPO stimulate hematopoiesis and improve hematologic abnormalities in these patients.
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PMID:Hematologic response in patients with aplastic anemia after long-term administration of recombinant human granulocyte colony-stimulating factor and erythropoietin. 944 48

In myelodysplastic syndromes (MDS), pancytopenia leads to a high risk of infectious and hemorrhagic complications. The progression to acute myeloid leukemia adds to morbidity and mortality. While transfusions of red blood cells and platelets are still a cornerstone of the therapy, the clinical use of recombinant hematopoietic growth factors has enlarged the range of therapeutic applications in patients with MDS. It is possible to reverse neutropenia by administration of G-CSF (granulocyte colony stimulating factor) or GM-CSF (granulocyte-monocyte colony stimulating factor). In the case of a severe infection, therapeutic administration of G-CSF together with antibiotics might be justified in otherwise neutropenic MDS patients. Since especially patients with only slight impairment of erythropoiesis and no transfusion dependency have the highest response rates but need erythropoietin (EPO) the least, pharmacoeconomic analyses are urgently needed. Controlled randomized trials will have to ascertain wether 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:Treatment with growth factors in myelodysplastic syndromes. 956 32

Recent advances in the molecular genetics of myelodysplastic syndromes (MDS) have shed new light on the pathogenesis of MDS allowing a better understanding of the defects of differentiation of the transformed clone and suppression of normal hematopoiesis. The clinical hematologist, however, continues to be challenged with the treatment of patients with 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. While prophylactic administration of G-CSF or GM-CSF cannot be recommended, treatment of febrile neutropenia might benefit from administration of G-CSF in addition to antibiotics. Administration of high-dose erythropoietin will improve erythropoiesis in around 20% of the patients, mainly in those with rather preserved erythroid function and no or low transfusion need. Coadministration of erythropoietin with either G-CSF or GM-CSF could increase the response rate. Allogeneic stem cell transplantation still is the only curative treatment and prolongs survival. Intensive chemotherapy for advanced MDS is possible with an acceptably low rate of early death and a complete remission rate between 45% to 60%, while initial results of autologous transplantation are promising.
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PMID:Clinical use of hematopoietic growth factors in the myelodysplastic syndromes. 957 Jun 76

The use of hematopoietic growth factors, although well established for the management of chemotherapy-induced neutropenia, remains controversial for the treatment of aplastic anemia and inherited bone marrow failure syndromes. The most commonly used factors are granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and erythropoietin. Newer growth factors such as stem cell factor, thrombopoietin, Flt3 ligand, and interleukins have shown promising results in the laboratory, and some have been used in clinical trials. This article reviews the clinical use of old and new hematopoietic growth factors in acquired and inherited bone marrow failure, and discusses emerging concerns about long term toxicity of these factors.
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PMID:Hematopoietic growth factors for the treatment of aplastic anemia. 966 65

Although all blood cells are derived from hematopoietic stem cells, the regulation of this production system is only partially understood. Negative feedback control mediated by erythropoietin and thrombopoietin regulates erythrocyte and platelet production, respectively, but the regulation of leukocyte levels is less well understood. The local regulatory mechanisms within the hematopoietic stem cells are also not well characterized at this point. Because of their dynamic character, cyclical neutropenia and other periodic hematological disorders offer a rare opportunity to more fully understand the nature of these regulatory processes. We review the salient clinical and laboratory features of cyclical neutropenia (and the less common disorders periodic chronic myelogenous leukemia, periodic auto-immune hemolytic anemia, polycythemia vera, aplastic anemia, and cyclical thrombocytopenia) and the insight into these diseases afforded by mathematical modeling. We argue that the available evidence indicates that the locus of the defect in most of these dynamic diseases is at the stem cell level (auto-immune hemolytic anemia and cyclical thrombocytopenia seem to be the exceptions). Abnormal responses to growth factors or accelerated cell loss through apoptosis may play an important role in the genesis of these disorders.
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PMID:Cyclical neutropenia and other periodic hematological disorders: a review of mechanisms and mathematical models. 1038 93

Irradiation is known to cause temporary to permanent marrow aplasia in cancer patients when administered as a sole therapy or in combination with chemotherapy. Until now, no studies have been carried out evaluating the haematological toxicities of involved field radiation administered post autologous stem cell transplantation (ASCT). We assessed bone marrow (BM) toxicity in 93 patients who received involved field radiation post ASCT (non-Hodgkin's lymphoma 21, Hodgkin's disease 7, breast cancer 15, and other solid tumours 50. Severe BM toxicity, with grade IV neutropenia, and/or thrombocytopenia, and/or anaemia necessitating interruption of radiotherapy for more than a week, was observed in 11 patients (malignant lymphoma-8 of which 7 were NHL, and 1 HD, breast cancer-1, Wilm's tumour-1, Ewing's sarcoma-1). Patients with malignant lymphoma were at higher risk of developing post ASCT radiation-induced cytopenias than patients with breast cancer or solid tumours, 28% vs 4.5%, respectively (P < 0.05). Of the 11 patients, 7 developed bacterial sepsis and 10 were hospitalised. The radiation-induced cytopenia patients necessitated platelets and red blood cell transfusions, interrupting the course of irradiation. Of the patients suffering from non-Hodgkin's lymphoma, 8/14 (57%) of those who received conventional courses of radiotherapy relapsed compared to 6/7 (86%) of those who received interrupted radiotherapy (P < 0.05). The most appropriate timing for radiation in malignant lymphoma patients who are scheduled for ASCT, as well as the protective role of haematopoietic growth factors like erythropoietin and Granulocyte (G) or Granulocyte-Monocyte (GM), colony stimulating factors (CSF) and others, are discussed.
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PMID:Involved field radiation post autologous stem cell transplantation in lymphoma patients is associated with major haematological toxicities. 978 19

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated with many risks, including immunosuppressive effects that may increase the risk of tumour recurrence. Many clinical studies have shown that epoetin (recombinant human erythropoietin) therapy can ameliorate, or even prevent, the anaemia associated with chemotherapy and cancer (including solid tumours as well as multiple myeloma or lymphoma). Response, defined as a significant (>50%) reduction in the rate of transfusions and/or a significant (>2 g/dl) elevation of haemoglobin levels, is usually observed in about 60% of the patients, irrespective of the type of standard chemotherapy given. The decrease in transfusion requirements is the major objective of epoetin therapy, because they are costly, inconvenient and are associated with potential adverse effects. Epoetin therapy also brings about substantial improvements in various indices of quality of life that are proportional to changes in haemoglobin level. However, large dosages of epoetin are generally required and about 40% of patients do not respond even to very high dosages. A number of adverse effects of epoetin therapy have been observed in patients with renal failure. The most prominent include hypertension, headaches, seizures and thrombotic events. These complications can also occur in patients with renal failure who are not receiving epoetin. Their exact incidence has been assessed in placebo-controlled studies, which have demonstrated that there is no increased risk of thrombosis or seizure with epoetin. However, it is now generally accepted that 10 to 20% of haemodialysis patients will experience an elevation of blood pressure because of epoetin and there is no doubt that a rapid elevation of blood pressure may cause generalised seizures. In other settings, including anaemia associated with cancer, very few adverse effects have been attributed to epoetin. However, close monitoring of blood pressure should be implemented in patients with hypertension. There is no evidence that epoetin stimulates tumour growth. With the dosages of epoetin currently used, there is no evidence of stem cell competition, resulting in thrombocytopenia or neutropenia, or of stem cell exhaustion, producing secondary anaemia when treatment is stopped. Epoetin is a remarkably well tolerated drug that offers significant benefits in patients with cancer.
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PMID:A risk-benefit assessment of epoetin in the management of anaemia associated with cancer. 980 42

Betafectin PGG-glucan is a novel beta-(1,3)glucan that has broad-spectrum anti-infective activities without cytokine induction. Here we report that PGG-glucan also has both in vitro and in vivo hematopoietic activities. In vitro studies with bone marrow target cells from the C3H/HeN mouse revealed that although PGG-glucan alone had no direct effect on hematopoietic colony-forming cell (CFC) growth, when combined with granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF, it increased CFC numbers 1.5- to 2.0-fold over those obtained with CSFs alone. Bone marrow cells cultured for high-proliferative-potential CFCs in the presence of interleukin (IL)-1, IL-3, macrophage CSF, and stem cell factor (SCF), or cultured for erythroid burst-forming units in the presence of IL-3, SCF, and erythropoietin, also exhibited enhanced growth in the presence of PGG-glucan. The synergistic effect of PGG-glucan was specific and could be abrogated by anti-PGG-glucan antibody. The ability of PGG-glucan to modulate hematopoiesis in vivo was evaluated in myelosuppressed rodents and primates. C3H/HeN female mice were intravenously administered saline solution or PGG-glucan (0.5 mg/kg) 24 hours before the intraperitoneal administration of cyclophosphamide (200 mg/kg), and the recovery of bone marrow cellularity and granulocyte-macrophage progenitor cells was evaluated on days 4 and 8 after cyclophosphamide treatment. At both time points, enhanced hematopoietic recovery was observed in PGG-glucan-treated mice compared with saline-treated control mice. In a final series of in vivo experiments, we evaluated the ability of therapeutically administered PGG-glucan to enhance hematopoietic recovery in cyclophosphamide-treated cynomolgus monkeys. Monkeys received intravenous infusions of cyclophosphamide (55 mg/kg) on days 1 and 2, followed on days 3 and 10 by intravenous infusion of PGG-glucan (0.5, 1.0, or 2.0 mg/kg). Compared with those in saline-treated monkeys, accelerated white blood cell recovery and a reduction in the median duration of neutropenia were observed in PGG-glucan-treated monkeys. These studies illustrate that PGG-glucan has both in vitro and in vivo hematopoietic activities and that this agent may be useful in the prevention and/or treatment of chemotherapy-associated myelosuppression.
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PMID:In vitro and in vivo hematopoietic activities of Betafectin PGG-glucan. 984 81

Carboplatin is one of the most common drugs used for radiochemotherapy of cancer. However, the best way to combine the drug with fractionated radiotherapy has not been established. In the present study the authors investigated which maximum tolerated daily bolus dose of carboplatin would allow safe radiopotentiation for 10 consecutive radiotherapy days, the scheme being repeated twice during the 6 weeks that a conventional radiotherapy scheme lasts. Seventy-two patients with lung or pelvis malignancies were included in a dose escalation study. Twenty-four patients comprised the first baseline cohort and were treated with radiotherapy alone. The daily dose of carboplatin was escalated starting from 38 mg/m2 daily (for 10 days) and increasing by 7 mg/m2 per day. Six patients were to be included in each cohort. All 12 patients treated at the 38 mg/m2 and 45 mg/m2 dose level completed two cycles of 10-day carboplatin treatment with no grade III-IV toxicity. Granulocyte colony-stimulating factor effectively averted the incidence of neutropenia and allowed the administration of the second carboplatin 10-day cycle in five of six patients at the 52 mg/m2 daily dose level. Platelet grade III-IV toxicity was observed in all 12 patients (six supported with granulocyte colony-stimulating factor and six with granulocyte colony-stimulating factor and recombinant human erythropoietin) treated at the 59 mg/m2 daily dose level and none of them received the second cycle of chemotherapy. Twelve patients were treated at the same dose level using amifostine 500 mg before carboplatin infusion. Two patients interrupted chemotherapy because of severe nausea and vomiting. Nine of 10 who accomplished the 10-day treatment had platelet levels more than 90,000/microl on day 28 and completed the second 10-day cycle without severe toxicity. Acute radiation toxicity did not increase in the carboplatin cohorts. In this study the authors established a high-dose fractionated carboplatin schedule that can be safely administered during radical radiotherapy.
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PMID:Fractionated carboplatin radiosensitization: a phase I dose-escalation study. 985 62

There are several therapeutic options for myelodysplastic syndrome (MDS) patients but the potentially curative ones are only available for a minority of individuals. At present, in fact, the only two treatments that can prolong survival are allogeneic stem cell transplantation and intensive chemotherapy. The only two haematopoietic growth factors that can be useful in the treatment of selected MDS patients are recombinant human erythropoietin (rHuEpo) and G-CSF. Overall 15 to 20% of patients with MDS respond to rHuEpo treatment but the vast majority of responders are not transfusion-dependent and the doses required to achieve response are > 450 IU/kg per week. Factors predicting response include serum Epo levels <100 mU/ml, female gender and no or low need for transfusion. Recognising potential responders to rHuEpo can be extremely important in individual cases of MDS. G-CSF alone should be used only for short-term treatments. It may be administered to individual patients during an infective episode that does not respond to antibiotic therapy, particularly in the case of fungal infections. In addition, G-CSF may be employed for shortening the length of severe neutropenia following intensive chemotherapy. American and Scandinavian studies have shown that about 40% of MDS patients respond to a combined treatment of rHuEpo with G-CSF with amelioration of anaemia and that response can be maintained for a median duration of 24 months. Using pre-treatment serum Epo levels as a ternary variable (<100, 100-500 or > 500 U/l) and red blood cell transfusion need as a binary variable (<2 or > or =2 units per month), a predictive score for erythroid response to G-CSF plus rHuEpo can be obtained. This score can identify patients with a high probability of erythroid responses (about 75%). Due to the inadequacies of all current treatment modalities, participation in clinical trials should always be encouraged.
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PMID:Haematopoietic growth factors in the treatment of myelodysplastic syndromes. 1010 Dec 10


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