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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases.
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PMID:Therapeutic aspects of myelodysplastic syndromes in chronic phase. 131 Jan 27

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

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

We treated 10 patients with a therapy-related myelodysplastic syndrome with escalating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) in a phase II trial and used sequential cytogenetic analyses to determine whether there was stimulation of nonclonal hematopoiesis. The GM-CSF was administered by continuous intravenous infusion over 2 hours daily for 14 days, followed by a 14-day rest period. The initial starting dose was 60 micrograms/m2/d. The GM-CSF dose was escalated within individual patients to 125 micrograms/m2, 250 micrograms/m2, and then 500 micrograms/m2/d until the peripheral blood neutrophil count at least doubled and exceeded 1,000/microL. GM-CSF treatment then continued in monthly maintenance cycles. During 57 treatment courses, the neutrophil count increased in 52 but only doubled and exceeded 1,000/microL in 21. Mild eosinophilia was stimulated in five patients, but only two had greater than 1,000 eosinophils/microL. In only three patients was any stimulation of platelet or red blood cell production observed, and thus, little change in transfusion requirements occurred. The bone marrow karyotypes from individual patients either remained completely abnormal or became increasingly abnormal over the course of treatment. We found no evidence that GM-CSF preferentially stimulated normal marrow stem cells to proliferate or had the ability to eradicate the cytogenetically abnormal clone by inducing terminal differentiation. Although the effect on granulopoiesis was transient and dependent on continued GM-CSF treatment, the increase in the neutrophil count was clinically important in some patients, allowing more effective control of ongoing infections.
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PMID:Clinical and cytogenetic responses to granulocyte-macrophage colony-stimulating factor in therapy-related myelodysplasia. 142 69

Subcutaneous administration of recombinant human Interleukin-1 beta (IL-1 beta) in a dose of 1-3 x 10(4) U/day for 14 to 72 days resulted in an increase in circulating granulocytes and bone marrow monocytes in all the 4 patients examined. Circulating platelet count was also increased in two of four patients with myelodysplastic syndrome (MDS) and aplastic anemia (AA). Bone marrow examination revealed an increase in megakaryocyte count in these patients, whereas the percentage of blast was not changed. An increase in blood platelet count was accompanied by an increase in serum GM-CSF in a patient with AA, whereas serum IL-6 level was not changed throughout the treatment with IL-1 beta. These findings suggest that IL-1 beta may be useful for the treatment of a proportion of patients with MDS and AA who are associated with thrombocytopenia.
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PMID:[Effect of subcutaneous administration of interleukin-1 beta on blood platelet count and serum GM-CSF in patients with myelodysplastic syndrome and aplastic anemia]. 143 38

In a phase II study, 21 patients with MDS (RAEB, RAEBt, CMML and RA and RAS with severe cytopenia) were randomized to be treated with 3 courses of GM-CSF (3 micrograms/kg/day s.c.) alone (11 patients) or in combination with AraC (20 mg/m2/d s.c.) (10 patients) for 14-d periods, interrupted by 14-d rest periods. Eight patients discontinued the treatment. In the GM-CSF group a marked increase in WBC and neutrophil counts during each course of treatment administration were seen in most patients. Platelet counts decreased in 14 of 24 courses of treatment in the GM-CSF plus AraC group but in none of the GM-CSF group. Although the changes in the circulating blood cells were transient and the counts tended to return to the pretreatment levels during the rest periods, some more durable effects were seen. In 3/6 patients of the GM-CSF group who completed the designed treatment, both WBC and neutrophils remained elevated above the pretreatment levels throughout the 3-month period of treatment, while in one of them thrombocytopenia improved considerably. In the GM-CSF plus AraC group, 4 out of the 7 patients who completed the treatment showed an improvement of neutropenia as well as anaemia. In these 4 patients the BM percentage of blasts was also decreased. In conclusion, the results of this study indicate that GM-CSF given intermittently improves leukopenia in some patients with MDS. In addition, the administration of GM-CSF seems to prevent granulocytopenia of concurrent AraC treatment and may be of benefit in the treatment of these diseases.
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PMID:Treatment of myelodysplastic syndromes with human granulocytic-macrophage colony stimulating factor (GM-CSF) or GM-CSF combined with low-dose cytosine arabinoside. 144 28

Hypoplastic acute leukemia (HAL) is characterized by pancytopenia and by hypocellularity of the bone marrow. The marrow contains equal to or more than 30% myeloblasts. Absence of tissue infiltrates and/or tumor masses is mandatory. Eight patients are described here. They do not fit into the FAB classification for either acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS), except for one patient who subsequently proved to have a chronic myelomonocytic leukemia (CMML). The median age is 65 years. Two patients, including the CMML patient, are alive, 22 and 6 months from diagnosis. Six patients have died. The median survival is 8 months. Normal bone marrow cells cultured either with HAL sera or with HAL peripheral blood mononuclear cells as feeders and exogenous GM-CSF yielded subnormal CFU-GM counts. This might indicate inhibitory activity of HAL serum and defective stimulatory activity of HAL peripheral blood mononuclear cells.
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PMID:Hypoplastic acute leukemia: description of eight cases and search for hematopoietic inhibiting activity. 145 85

The majority of patients suffering from myelodysplastic syndromes (MDS) die of complications due to cytopenia. Clinical trials have demonstrated that in an essential number of MDS patients cytopenia can be ameliorated by exogenously supplied growth factors. We investigated endogenous serum levels of GM-CSF and IL-3 in 15 healthy individuals and 34 patients suffering from MDS. No circulating growth factors were detected in the serum of healthy controls, nor was IL-3 measurable in MDS patients. GM-CSF serum levels, however, were elevated in a significant number of patients (26.5%). Levels did not correlate with FAB classification, leukocyte count or chromosomal abnormalities. No significant differences in GM-CSF or IL-3 receptor expression were detected between healthy individuals and MDS patients. One patient with increased endogenous GM-CSF serum level and normal surface receptor expression responded to exogenously applied GM-CSF. In the light of these results, a functional alteration of growth factor receptors or disturbances of signal transduction pathways must be discussed for MDS.
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PMID:Endogenous serum levels and surface receptor expression of GM-CSF and IL-3 in patients with myelodysplastic syndromes. 146 26

Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.
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PMID:Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF). The EORTC Leukaemia Group. 149 35

In conclusion, hematopoietic growth factors have been shown to enhance the recovery and function of circulating WBCs after standard-dose cancer therapy or high-dose cancer therapy with ABMT, and preliminary data strongly suggests that these agents may have the ability to restore leukocyte numbers and competence in AIDS, myelodysplastic syndromes, and other marrow failure states. Phase I and II trials of GM-CSF in patients with AIDS, cancer, marrow failure states, and following bone marrow transplantation have been published, and limited phase III randomized trial experiences have been reported as well. Overall, GM-CSF represents a fascinating molecule with which to modulate human hematopoiesis in vivo. The multilineage stimulatory effects of GM-CSF that are evident in vitro have not been striking or consistent in clinical trials. However, the effects of GM-CSF on the production and function of mature neutrophils, monocytes, and eosinophils have been noted in the vast majority of clinical scenarios in which this cytokine has been tested. The clinical benefits of GM-CSF have, to date, only been proven in large-scale randomized studies of recovery from ABMT for lymphoid neoplasms. However, further data regarding the use of GM-CSF in other clinical settings have been generated, and the final results are eagerly anticipated by the oncology community. The beneficial effects of GM-CSF following ABMT consisted not only of a shorter period of absolute neutropenia, but also fewer significant infections, a diminished requirement for intravenous antibiotic administration, and a shorter overall duration of inpatient hospitalization. The use of GM-CSF in clonal disorders of hematopoiesis, such as myelodysplasia or myeloid leukemias, requires caution before such applications can be routinely recommended, and the demonstration of safety in this setting from large randomized trials will be needed. Preliminary data from small randomized trials suggests that the incidence of evolution to leukemia in patients with myelodysplasia and the number of patients with regrowth of leukemia after induction treatment in relapsed patients with AML may not be significantly different than in patients who do not receive GM-CSF. Various neutropenic conditions (eg, idiopathic or congenital) may respond clinically to hematopoietic growth factors such as GM-CSF. Patients treated for 3 to 15 months continue to respond with significantly increased granulocytes and resolution of prior infection. The subcutaneous route of administration is convenient and patients seem to accept it readily. It is difficult to determine the extent to which adjunctive therapy with GM-CSF will be cost effective.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF): preclinical and clinical investigations. 150 75


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