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)

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

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

We have tested granulocyte/macrophage-colony-stimulating-factor (rhGM-CSF, fully glycosylated, Sandoz, Schering/Plough) in 40 patients with chemotherapy-induced neutropenia. The drug enhanced leukocyte recovery in 5 different dose levels (2-32 micrograms/kg body weight) if given by continuous intravenous infusion or subcutaneously for 5 days. Patients who received rhGM-CSF during neutropenic infections (n = 32) survived significantly better if they recovered leukocytes to at least 1.5 x 10(9)/l. In patients with myelodysplastic syndromes and excess of blasts (n = 82) remission could be induced in nearly 50% if the drug was given together with low dose cytosine arabinoside (LD-AraC). The results of these phase-II-studies show that rhGM-CSF is a safe drug which may save many patients from life-threatening situations during haematopoietic insufficiency.
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PMID:[Growth factors in therapy of life threatening leukopenia]. 162 26

We treated 47 adult patients with de novo myelodysplastic syndrome (MDS) by an anthracycline-AraC regimen. Median age was 54, and M/F 1.3. At diagnosis, 26 patients had refractory anaemia with an excess of blasts in transformation (RAEB-T) three had refractory anaemia (RA), 11 had refractory anaemia with excessive blasts (RAEB) and seven had chronic myelomonocytic leukaemia (CMML). Treatment was started within 3 months of diagnosis in 30 patients, and after more than 3 months in the 17 remaining patients. At the onset of treatment, 16 patients had progressed to acute myeloid leukaemia (AML). Twenty-two patients (47%) reached complete remission (CR), 10 (21%) had hypoplastic death and 15 (32%) had resistant disease. Median actuarial disease-free interval was 11 months. Median actuarial survival was 14 months from diagnosis and 10 months from the onset of treatment. A significantly higher CR rate was found in patients with RAEB-T at diagnosis (69% v 19% in patients with other FAB subtypes: P = 0.008), and in patients treated within 3 months of diagnosis. Using multivariate analysis, RAEB-T at diagnosis emerged as the most powerful prognostic factor of CR achievement. Karyotype was the only significant prognostic factor of disease-free interval, with a median of 16.5 months in patients with normal karyotype versus 4 months in patients with normal findings (P = 0.018). A subgroup of 15 patients with RAEB-T at diagnosis and normal karyotype, who had a CR rate of 80% and a median actuarial disease-free interval of 18 months, could be identified. Our results confirm that, overall, intensive chemotherapy has limited efficacy in MDS, especially when compared with allogeneic bone marrow transplantation (BMT). Relatively favourable results were obtained in our patients with RAEB-T at diagnosis, however, particularly those with normal karyotype. In that subgroup, intensive chemotherapy may be recommended, especially before BMT, as a high risk of relapse after BMT in patients with RAEB-T allografted as first line therapy has been reported.
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PMID:Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy. 202 75

Based on the in vitro experiments which showed the capacity of Aracytine (AraC) to induce differentiation of leukemic cells, low dose AraC treatment of patients with acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS) has been available since 1980. Many studies involving only small numbers of patients have demonstrated contradictory results regarding the efficacy or the mechanism of action of this regimen. A retrospective clinical study is presented, including 159 patients treated in 11 French institutions and 1 German institution (AML: 99 patients; MDS: 38 patients). The study confirms the efficacy of low dose AraC, especially in elderly patients with hypoplastic AML. Although, less severe than with high dose chemotherapy, toxicity needs regular monitoring. The mechanism of action cannot be ascertained by this clinical study, however half of the complete remissions were obtained with no bone marrow aplasia. Studies with low dose AraC and/or other in vitro differentiating agents need to be continued.
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PMID:[Treatment of malignant hemopathies with aracytine in low doses. Analysis of 159 cases]. 386 52

We treated a 16-month-old girl with myelodysplastic syndrome (MDS; refractory anemia with excess of blasts subtype, RAEB by FAB classification) that developed into acute megakaryoblastic leukemia (ANLL-M7). The blast cells were positive for CD41 shown by flow cytometry and for platelet peroxidase by electron microscopy. Cytogenetically, five kinds of abnormal karyotypes were apparent at the initial visit and karyotypic progression (clonal evolution) was also evident. These karyotypes were considered to be derived from the putative original clone, 48,XX, +6, +21. The observed karyotypes were considered 50,XX, +4,add(4)(q31), +6,add(7)(p22),add(10)(q24),add(12)(q11), +20, +21, + mar[karyotype A];48,XX,add(4)(q31), +6,add(10)(q24),add(12)(q11), +21 [karyotype B];48,XX, +6,t(6;13)(p23;q14), +21 [karyotype C];51,XX, +X, t(6;13)(p23;q14), + der(6)t(6;13)(p23;q14), +21, +21, + mar [karyotype D]; and 49,XX, +X, -3,t(6;13)(p23;q14), +der(6)t(6;13)(p23;q14), -12, +21, +21, + mar [karyotype E]. It seems karyotypes B and C were derived from the putative clone; karyotype B developed into karyotype A; and karyotype C developed into karyotype E through karyotype D. After development of ANLL-M7, the cytogenetic study showed a karyotype with further karyotypic progression. The patient was treated with high-dose cytosine arabinoside (HD AraC) followed by allogeneic bone marrow transplantation. Despite intensive care, she died 3 months after the transplantation.
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PMID:Childhood myelodysplastic syndrome with clonal evolution progressing to acute megakaryoblastic leukemia (ANLL-M7). 822 7

In an attempt to reestablish normal hematopoiesis in symptomatic myelodysplasia (MDS) and to show the tolerability of a combination treatment of low-dose cytosine arabinoside (LD AraC) and interleukin-3 (IL-3), we treated 31 patients (pts., median age 65 years) who had more than 10% blasts in the bone marrow (BM) and hematopoietic failure with LD AraC (2 x 10 mg/m2 sc, day 1-14) plus IL-3 (once daily sc, day 8-21) at different dose steps (1.0, 2.5, 5.0, and 10.0 micrograms/kilogram body weight). The numbers of each 21-day cycle varied between 1 (3 pts.), 2 (6 pts.), 3 (8 pts.), 4 (1 pt.), 5 (5 pts.), and 6 (8 pts.), in total 116 cycles on an outpatient basis. Subjective tolerability was good in 20 cases (65%). Toxicities were fever (29 pts.), flu-like symptoms (17 pts.), infections (15 pts.), hepatic toxicity (10 pts.), and skin reactions (8 pts.). Overall response was seen in 13 cases (42%) and 5 complete responses (CR), while 10 pts. had stable disease (SD), 5 progressed (2 to acute leukemia), 2 were considered toxic deaths, and 1 died due to the disease. Median survival is 18 months, progression-free survival is 12.5 months (18.0 months in responding pts.), with an actuarial follow-up of 31 months. The data from this phase I/II study show that a combination of LD-AraC and IL-3 is well tolerated and that stable responses can be achieved in MDS by means of an easy outpatient therapy.
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PMID:Interleukin-3 plus low-dose cytosine arabinoside for advanced myelodysplasia: a pilot study. EORTC Leukemia Group. 868 23

Homoharringtonine (HHT) is a cytotoxic alkaloid isolated from the evergreen tree cephalotaxus harringtonia native to the southern provinces of China. The principal mechanism of action of HHT is the inhibition of protein synthesis in a dose- and time-dependent manner by acting on the ribosomes of cancer cells. It blocks the progression of cells from G1 phase into S phase and from G2 phase into M phase. It is synergestic or additive in vitro with AraC, amsacrine, actinomycin D and dexamethasone. Clinical studies have indicated that HHT is effective in treating acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS), but not acute lymphoblastic leukemia (ALL) and solid tumors. The dose limiting toxicities are hypotention and myelosuppression. Homoharringtonine has relatively mild extramedullary toxicities and no anthracycline-like cardiac toxicity, which make it a suitable candidate for the treatment of aged patients. Pharmacological studies indicate that HHT belongs to the category of multidrug resistance (MDR)-related drugs. The cells resistant to HHT are cross-resistant to anthracycline, vinca alkaloids, mitoxantrone, but not cis-platine and AraC. Multiple mechanisms, including the sequential emergence of overexpression of multidrug resistance-associated protein (MRP) and MDR1 genes, are involved in the cross-resistance of tumor cells to HHT.
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PMID:Homoharringtonine: an effective new natural product in cancer chemotherapy. 874 64

Evaluating the proliferative activity of the immature erythro- and myelopoiesis as well as the mature myelopoiesis in 21 MDS patients and 14 healthy controls by simultaneously staining bone marrow cells for surface phenotype and DNA content, we found the percentages of proliferating S-phase cells in the early stage of MDS were higher. With disease progression evaluated by the FAB classification this parameter decreased significantly for both the immature myelo- and erythropoiesis. Evaluation of the proliferative activity of the mature myelopoiesis defined by the CD66 antigen revealed no difference between the normal controls and the MDS patients. Using another assay simultaneously labelling bone marrow cells for three leucocyte differentiation antigens during treatment with GM-CSF and low-dose AraC the cells clearly differentiated in one case. In another patient the disease seemed to progress as evaluated by cells only expressing immature antigens. The above mentioned immunophenotypic changes persisted at least one month after termination of treatment. In conclusion, the evaluation of proliferation and differentiation of leucocyte subsets using multiparameter flowcytometric assays in myelodysplastic patients from different FAB groups before as well as during treatment with haemopoietic growth factors may prove valuable in the future.
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PMID:Myelopoiesis in myelodysplasia evaluated by multiparameter flow cytometry. 875 Jun 19

The major vault lung resistance protein LRP is a cytoplasmic protein involved in drug resistance, especially in acute myeloid leukemia. We looked for LRP overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66% of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+) in 33% of the cases. No correlation was seen between LRP overexpression and FAB type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts. Furthermore, in the 18 cases treated with anthracycline-AraC intensive chemotherapy and the 7 cases treated with low dose AraC, the response rate was not significantly different in LRP+ and LRP- patients. Survival was also similar in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more frequent in MDS than in de novo AML and, as in AML, is only partially correlated with PGP expression. In our experience, however, LRP was not a prognostic factor for response to chemotherapy and survival in MDS.
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PMID:Expression of lung resistance protein and correlation with other drug resistance proteins and outcome in myelodysplastic syndromes. 964 68


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