Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte colony-stimulating factor (G-CSF) has strong leukopoietic activity and it is used for patients with leukopenia during leukemia chemotherapy. However, some leukemia cells show a high affinity to G-CSF and are driven to proliferative phase. In our laboratory, we developed two testing methods. 1) Flow cytometric method on G-CSF susceptibility of leukemia cells using FITC-labeled G-CSF, and 2) Immunohistochemical method for detecting the ratio of cells driven from dormant phase to proliferative phase by G-CSF with anti-PCNA antibody and Ki-67 antibody. In MDS patients G-CSF administration induced an increase of cells in proliferative phase. The patients treated with cytosine arabinoside following G-CSF showed hematologically good improvement. A new mode of therapy using G-CSF in combination with other cytokines or antileukemic agents will be developed in the near future for treatment of leukemia patients.
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PMID:[Recent trend in G-CSF therapy and clinical laboratory tests]. 128 10

Clinical trials with hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF], interleukin-3, erythropoietin] have been done in patients with myelodysplastic syndromes. Treatment with GM-CSF or G-CSF has resulted in an increase of neutrophil counts into the normal range in the vast majority of patients. Progression to acute leukemia does not appear to occur more frequently in the patients receiving GM-CSF or G-CSF. Increases in platelet counts and hemoglobin levels have been reported after treatment with interleukin-3 and erythropoietin, respectively, although the response is only seen in a minority of treated patients. Combination therapy with GM-CSF and low-dose cytosine arabinoside has been studied, but present data do not indicate an advantage over other treatment strategies. Cytogenetic and molecular genetic analyses demonstrate that both normal and malignant precursor cells are stimulated by cytokine therapy.
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PMID:Treatment of myelodysplastic syndromes with cytokines and cytotoxic drugs. 137 66

Filgrastim (granulocyte colony stimulating factor) recently became commercially available for the treatment of chemotherapy-induced neutropenia. Studies have shown that filgrastim induces a dose-dependent granulocytosis in humans, thereby shortening the period of neutropenia in patients treated conventionally with submarrow ablative doses of chemotherapy, as well as with marrow ablative therapy given in the bone marrow transplant setting. By reducing the incidence and severity of infections and mucositis in patients treated with chemotherapy, it has a significant economic impact since it shortens the duration of antibiotic administration and hospitalization. Adverse reactions reported are limited to mild to moderate bone pain. Several other potential applications are being investigated for filgrastim, including treatment of patients with myelodysplastic syndrome and congenital neutropenia.
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PMID:Topics in clinical pharmacology: filgrastim, a myeloid colony stimulating factor. 137 51

Clinical trials with hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF], interleukin-3, or erythropoietin) have been performed on patients with myelodysplastic syndromes. Absolute neutrophil counts can be readily raised to within the normal range by treatment with GM-CSF or G-CSF. Increases in platelets and hemoglobin have been reported after treatment with interleukin-3 and erythropoietin, respectively. Cytogenetic and molecular genetic analyses have demonstrated that both normal and malignant precursor cells are stimulated by cytokine therapy.
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PMID:Treatment of myelodysplastic syndromes with hematopoietic growth factors. 137 94

Patients with myelodysplastic syndromes frequently present with anemia, leukopenia and thrombocytopenia due to defective maturation of bone marrow cells. Clinical studies with hematopoietic growth factors, including interleukin-3 (IL-3), have been undertaken to evaluate the possibility to reverse cytopenia. In initial phase I/II trials, treatment with IL-3 has resulted in an increase of neutrophil counts in 59%, of platelet counts in 34%, and in reticulocyte counts in 25% of the patients. Adverse effects were rather mild but in individual patients a reversible decrease in platelet counts and in the number of blast cells in blood and bone marrow were observed. Further clinical trials should concentrate on the combination of an early acting cytokine like IL-3 and later acting hemopoietic growth factors like erythropoietin and granulocyte colony-stimulating factor.
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PMID:Interleukin-3 in the treatment of myelodysplastic syndromes. 152 Sep 8

Hematopoietic growth factors, particularly granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, can be used as supportive agents to enhance bone marrow recovery after the administration of myelosuppressive chemotherapy given for nonmyeloid neoplasms. The use of these agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome poses novel opportunities and challenges due to their direct effects on the neoplastic cells, which represent the transformed counterparts of normal hematopoietic stem cells. The interaction between hematopoietic growth factors and leukemic progenitor cells bearing a specific receptor for a given agent would be expected to result in proliferation, although maturation induction could occur. Hematopoietic growth factors have been employed as primary differentiating agents in myelodysplastic syndrome and as supportive agents after chemotherapy in acute myeloid leukemia. In either case, close monitoring for evidence of leukemic stimulation is required. Alternatively, pretreatment with colony-stimulating factors could induce cell cycling, thereby making the leukemic cells more susceptible to S-phase-specific chemotherapeutic agents, such as cytarabine.
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PMID:Hematopoietic growth factors and leukemia. 159 Dec 93

In vitro marrow hemopoietic cultures were utilized to determine the possible efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) for treating the refractory cytopenias present in the myelodysplastic syndromes (MDS). Our studies showed responsiveness of enriched hemopoietic precursors in vitro to the proliferative and granulocytic differentiative stimuli of G-CSF, generally without increased clonal self-generation. These in vitro parameters correlated with in vivo hematologic responses in our Phase I and II clinical trials. In this study 18 patients were treated for two months with s.c. administration (0.1-3 micrograms/kg/day) of G-CSF, escalating doses every two weeks. This study indicated normalization of neutrophil courses in 16 patients and reticulocyte responses with decreased red blood cell (RBC) transfusion requirements in three of 12 transfusion-dependent patients. Marrow myeloid maturation improved in the responding patients. Extended treatment for additional six- to 16-month periods has indicated persisting neutrophil responses. The relative risk of developing bacterial infections was significantly decreased in patients whose neutrophil level normalized (absolute neutrophil count greater than 1,500/mm3) during G-CSF therapy, compared to such episodes in their pretreatment neutropenic period. This therapy was well-tolerated, without serious toxicity being noted. In vitro neutrophil function (chemotaxis and phagocytosis) remained normal or improved in six of the eight tested patients. Transformation to acute myelogenous leukemia occurred in two patients with refractory anemia with excess blasts in transformation (RAEB-T) during or within a month of the treatment period. Marrow cytogenetic studies indicate persistence of the initial normal and/or abnormal clones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of prolonged treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. 169 Dec 48

We present a patient with refractory anemia (RA) who developed Sweet's syndrome during the treatment of recombinant human granulocyte colony-stimulating factor (rhG-CSF). A 30-year-old man was admitted to the hospital for evaluation of anemia. He was diagnosed as MDS (RA). As a phase II study in MDS, rhG-CSF therapy was begun. Fever associated with cutaneous lesion developed over the left shoulder. Antibiotics showed no effects. Skin biopsy revealed Sweet's syndrome. This skin lesion disappeared thoroughly with discontinuance of G-CSF and administration of prednisolone. To examine whether Sweet's syndrome was related to the G-CSF therapy, we analyzed the effect of G-CSF on the function of patient's neutrophils. However, the function of patient's neutrophils was not activated by G-CSF administration.
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PMID:[Sweet's syndrome in patient with refractory anemia during recombinant human granulocyte colony stimulating factor therapy]. 169 95

Myelodysplastic syndromes (MDS) are characterized by chronic refractory cytopenias resulting in increased risk of infection, bleeding, and conversion to acute leukemia. In an effort to improve these cytopenias we have treated 18 patients over a 6- to 8-week period with increasing daily subcutaneous doses of recombinant human granulocyte colony-stimulating factor (G-CSF). Sixteen patients responded with improvement in neutrophil counts. On cessation of treatment these counts returned to baseline values over a 2- to 4-week period. To maintain these improved blood counts 11 patients were treated with G-CSF for more prolonged periods. Ten patients again responded with an increase in total leukocyte counts (1.6- to 6.4-fold) and absolute neutrophil counts (ANC) (3.6- to 16.3-fold), with responses persisting for 3 to 16 months. A significantly decreased risk of developing bacterial infections was noted during periods with ANC greater than 1,500/mm3 as compared with periods of time with ANC less than 1,500/mm3. Two anemic patients had a greater than 20% rise in hematocrit over the study period, and 2 additional patients had a decrease in red blood cell transfusion requirements during G-CSF treatment. Bone marrow myeloid maturation improved in 7 of 9 maintenance phase patients. Three patients progressed to acute myeloid leukemia during treatment. The drug was generally well-tolerated and no severe toxicities were noted. These data demonstrated that G-CSF administered to MDS patients by daily subcutaneous administration was well-tolerated and effective in causing persistent improvement of the neutrophil levels and marrow myeloid maturation. These effects were associated with a decreased risk of infection and, in some patients, with decreased red blood cell transfusion requirements.
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PMID:Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor. 169 2

Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.
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PMID:Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia. 169 46


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