Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently biotechnologic progress has, through the technique of the recombinant DNA, allowed a low cost production of large amount of several growth factors. Such a large availability has made possible to either carry out deeper investigations on the physiopathology of the hemopoietic regulation and perform new therapeutic approaches under different pathologic conditions. The most interesting acquisition concerning the biology of hemopoiesis to which such investigations have addressed us is the inadequacy of the protocols adopted till now. Such protocols considered only a simple vision of an elective action of a given growth factor during an exact maturation period of a determined cell colony. On the contrary, it was possible to point out a close network of inter-relationship among the different factors, which sometime impedes a clear distinction for each single factor, between actions of competence and progression in the cell maturation phenomena. However, the present uncertainty pertaining to the regulation of hemopoiesis has not impede the performance of clinical trials with positive findings in several pathologic conditions. The administration of recombinant erythropoietin has for example allowed to intervene in a resolutive way on the anemia in uremic subjects, and seems giving satisfactory results also in subjects with non renal origin anemic conditions. Satisfactory results were also obtained through the use of the Granulocyte-Macrophage CSF and of the Granulocyte-CSF, which by preventing neutropenia have allowed the performance of more adequate chemotherapeutic protocols in neoplastic subjects. New interesting perspectives are now coming for the use of Interleukin-3 in the treatment of the aplastic anaemia.
 ...
PMID:[Growth factors and hematopoiesis. Physiopathology and clinical applications]. 138 4

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates myeloid cell proliferation and maturation and enhances the function of terminally differentiated effector cells. Phase I and II clinical trials have demonstrated mild to moderate toxicities at doses of less than 30 micrograms/kg/day. These studies suggest a potential role for this growth factor to stimulate myelopoiesis in patients with aplastic anemia, myelodysplastic syndromes, AIDS, chemotherapy-induced myelosuppression, chronic neutropenia, and following bone marrow transplantation. The potential clinical uses of GM-CSF will depend on results of studies designed to optimize its therapeutic efficacy.
 ...
PMID:Clinical applications of human granulocyte-macrophage colony-stimulating factor. 177 Feb 27

The hematopoietic growth factor interleukin (IL)-3 is a potent regulator of blood cell proliferation. It promotes the survival, proliferation, and development of hematopoietic stem cells and committed progenitor cells of the granulocyte-macrophage, erythrocyte, eosinophil, basophil, megakaryocyte, mast cell, and lymphocyte lineages. In addition, IL-3 enhances mature myeloid cell functions such as phagocytosis and activation of basophils and eosinophils, as well as monocyte cytotoxicity. The first phase of clinical trials suggested that IL-3 may augment myelopoiesis in a number of clinical conditions. It may be efficacious for treatment of primary marrow disorders, including myelodysplastic syndromes and aplastic anemia. However, replacement therapy with IL-3 alone is probably not sufficient to obtain maximal stimulation of myelopoiesis. Preclinical and clinical studies published to date suggest that sequential use or combinations of growth factors will be needed to obtain optimal hematopoietic responses.
 ...
PMID:Interleukin-3. Its biology and potential uses in pediatric hematology/oncology. 178 68

In a phase I/II study, bone marrow biopsy specimens and aspirates of 20 patients with malignant tumors but normal bone marrow (n = 6), bone marrow failure resulting from chemotherapy (n = 4), myelodysplastic syndrome (n = 5), and aplastic anemia (n = 5) were evaluated before and after patients were treated with recombinant human interleukin-3 (rhIL-3). This cytokine proved to be an effective hematopoietic growth factor with only mild side effects. The rhIL-3 treatment led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells, except in most patients with aplastic anemia. In all patients, significant eosinophilia and, in some instances, bone marrow fibrosis developed. In addition to the increase in the number of circulating neutrophilic granulocytes, platelets, and reticulocytes, an increase of peripheral blood monocytes and lymphocytes was observed. The histologic and cytologic findings support the concept that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells. It appears to be a safe and efficient therapeutic modality in patients with bone marrow failure. Additional clinical studies are needed to determine which patients will profit most from rhIL-3 treatment.
 ...
PMID:Bone marrow findings after treatment with recombinant human interleukin-3. 199 45

Interleukin-3 (IL-3) is a T-cell-derived colony-stimulating factor (CSF) whose primary targets include relatively early, multipotential, hematopoietic progenitor cells. In this trial, we treated 24 patients with recombinant human IL-3 given by a daily 4-hour intravenous infusion for 28 days. The dose levels were 30, 60, 125, 250, 500, 750, and 1,000 micrograms/m2/d. At least three patients were entered at every dose level. Each participant suffered from bone marrow failure, with the underlying diagnosis being myelodysplastic syndrome (13 patients), aplastic anemia (eight patients), or aplasia after prolonged high-dose chemotherapy (three patients) for multiple myeloma, breast cancer, or acute myelogenous leukemia. Most patients tolerated therapy well, with the most frequent side effects being low-grade fever and headaches. Hematopoietic changes included modest increases in neutrophil counts (eight patients), eosinophil counts (six patients), platelet counts (three patients), and reticulocyte counts (two patients). An increase in blasts occurred in one patient who had refractory anemia with excess blasts in transformation and was reversible once IL-3 was discontinued. In addition, one patient with chronic myelomonocytic leukemia showed an increase in monocytes (and granulocytes). Progression to acute leukemia did not occur. Pharmacokinetic analyses showed a rapid clearance with a mean half-life of 18.8 minutes at the 60 micrograms/m2/d dose, and 52.9 minutes at the 250 micrograms/m2/d dose. Serum concentrations of 10 to 20 ng/mL of IL-3 were achievable at the 250 micrograms/m2/d dose. Our observations indicate that recombinant human IL-3 can be given safely at doses of 1,000 micrograms/m2/d or less. In addition, on the basis of preclinical data and the biologic activity observed in this study, further trials of this molecule, alone and in combination with other growth factors, are warranted in patients with pancytopenia.
 ...
PMID:Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. 204 65

Interleukin-3 (IL-3) is a glycoprotein belonging to the hematopoietic growth factor family that in preclinical in vitro and in vivo studies has exhibited a multilineage activity. Phase I/II trials with recombinant human IL-3 (rhIL-3) expressed in yeast are being done in patients with advanced malignancies as well as in patients with bone marrow failure states. Subcutaneous administration of rhIL-3 at dosages between 30 and 500 micrograms/m2 for 15 consecutive days has resulted in a dose-dependent increase in platelet counts as well as in a substantial increase in the number of circulating neutrophils, eosinophils, monocytes, and lymphocytes in patients with advanced malignancies but normal hematopoiesis. Erythropoiesis is less stimulated with an increase in hemoglobin concentration only in a minority of patients. In patients with secondary hematopoietic failure due to prolonged chemo-/radiotherapy or bone marrow infiltration by tumor cells, treatment with rhIL-3 leads to a clinically significant restoration of hematopoiesis, especially of thrombopoiesis and granulopoiesis. rhIL-3 has also been shown to improve neutrophil and platelet counts in patients with myelodysplastic syndromes, while improvement of hematopoiesis is rarely observed in patients with severe aplastic anemia with the presently used treatment schedules. Adverse effects of rhIL-3 are minor at the clinically used dosages and include fever, bone pain, headache, and stiffness of the neck. Transient thrombocytopenia has been observed in a few patients with myelodysplastic syndrome or aplastic anemia treated at dosages of 250-500 micrograms/m2. rhIL-3 is a multilineage hematopoietic cytokine with promising effects on platelet and neutrophil counts and special usefulness in patients with secondary hematopoietic failure.
 ...
PMID:Clinical effects of recombinant human interleukin-3. 204 66

In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained.
 ...
PMID:Effects of recombinant human interleukin-3 in aplastic anemia. 220 6

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
 ...
PMID:Hematopoietic hormones: from cloning to clinic. 267 59

Immune suppression of hematopoiesis has been implicated in the pathogenesis of acquired aplastic anemia. Similarly, abnormalities of T cells and bone marrow stromal cells have been reported in aplastic anemia, as has abnormal cytokine production. Stem cell factor (SCF) (also known as kit ligand, mast cell growth factor and Steel factor) is an early acting hematopoietic growth factor that is produced by a variety of mesenchymal cells including bone marrow stromal cells. To determine whether abnormalities in the production of stem cell factor occur in aplastic anemia, we evaluated serum levels of SCF in 25 patients with aplastic anemia. The mean serum levels of SCF in aplastic anemia patients were significantly lower (2.7 +/- 1.1 ng/ml) than those found in a comparable population of 257 normal controls (3.3 +/- 1.1 ng/ml) (P = 0.011). The SCF level did not correlate with patient age, the duration of aplastic anemia or with white blood cell count, platelet count or hematocrit. Although there is no direct evidence that lower SCF serum levels contribute to the pancytopenia seen in this disorder, identification of underlying abnormalities that can result in the deficient production of stromally derived hematopoietic growth factors will be important.
 ...
PMID:Serum stem cell factor levels in patients with aplastic anemia. 753 30

Aplastic anemia (AA) is a rare bone marrow (BM) disorder characterized by an unexplained failure of hematopoietic precursors to proliferate. In vitro growth of AA BM cells can be improved by the addition of the hematopoietic growth factor SCF (stem cell factor), which suggests that deficiency of SCF may be one of the underlying causes of the disease. In this study, we measured the concentration of SCF in sera of patients with severe AA. One hundred twenty-eight serum samples from 32 patients, at diagnosis and following therapy, were analyzed. Before treatment, SCF levels varied between 0.33 and 6.1 ng/mL; no correlation between hematopoietic function and SCF serum levels was apparent. Therapy with antilymphocyte globulin (ALG) or bone marrow transplantation (BMT) did not result in a recognizable pattern of changes in SCF levels. However, serum concentration of SCF in many patients with AA was at the low range of control serum levels determined in healthy blood donors. Of 128 AA serum samples tested before and after therapy, 107 were below the mean normal value of 3.3 ng/mL, including 26 samples below the minimum normal value of 1.3 ng/mL, as estimated in 267 controls. We also found that SCF levels in peripheral blood serum correlate well with factor concentrations in the BM plasma. Clinical observations suggest that higher SCF serum levels are often associated with a better clinical status of the patients in terms of survival and transfusion requirements. The data indicate that a deficient production of soluble SCF may contribute to AA in some patients; thus, suggesting a potential therapeutic benefit of SCF in this disorder.
 ...
PMID:Levels of soluble stem cell factor in serum of patients with aplastic anemia. 768 1


1 2 3 Next >>