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)

Thirteen cases, including 10 relapse cases, of refractory acute myeloid leukemia (AML) (aged 17-70, median 46) by cytosine arabinoside (Ara-C) combined with granulocyte colony-stimulating factor (G-CSF) simultaneously to enhance the sensitivity to Ara-C. Low dose Ara-C (10-40 mg/day) combined with G-CSF was administered in most of them. Complete (CR) and partial remission (PR) were achieved in 5 and 4 patients, respectively, and response (CR + PR) rate was 69.2%. We obtained 5 CRs and 3 PRs in 10 patients with relapsed AML. However, CR and PR duration was short in all cases. None of the 3 patients with MO, AML transformed from myelodysplastic syndrome (MDS), and de novo AML with trilineage myelodysplasia (TMDS) had any response. There was no leukemic colony formation in the culture medium containing G-CSF in the nonresponding patients. The combination therapy caused severe myelosuppression, and most patients experienced prolonged neutropenia, and suffered from infections. In some patients enhanced chemosensitivity of leukemic cells induced by G-CSF was indicated but, the effect of this approach must be determined by large scale controlled studies.
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PMID:[Trial of combined cytosine arabinoside with granulocyte colony-stimulating factor therapy or refractory acute myeloid leukemia]. 756 92

Plasma concentration of cytosine arabinoside (Ara-C) was determined in elderly patients with myelodysplastic syndromes or acute myelocytic leukemia who were treated with subcutaneous injection of Ara-C (Ara-C s.c.; 10 mg/m2/12 hr, 14-21 days), continuous drip infusion of Ara-C (Ara-C d.i.v.; 20 mg/m2/day, 24 hr 14 days) and/or oral administration of cytarabine ocfosfate (SPAC) (SPAC p.o.; 100 mg-300 mg/body/day, 14 days) by radioimmunoassay. In the Ara-C s.c. patients, the peak plasma level (Cmax) of Ara-C was 103 ng/ml and the time to reach Cmax was 15 min. The elimination half-like (t1/2) was 25 min and no accumulation was detected after 14 days of consecutive Ara-C s.c. administrations. In the SPAC p.o. patients, Cmax of Ara-C was 3-8 ng/ml and it took 3-5 days to reach Cmax. The plasma concentration level of Ara-C remains almost at the Cmax level during the SPAC p.o. administration and it remained higher than 0.32 ng/ml for as long as 15 days after the end of administration. In a Ara-C d.i.v. patient, plasma level of Ara-C was detected 4-7 ng/ml during the administration (day 7 through day 14). In all patients bone marrow suppression was observed after chemotherapy regardless of regimen, and there was no significant difference between nadir peripheral cell blood counts of Ara-C s.c. patients and SPAC p.o. patients.
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PMID:[Plasma concentration of cytosine arabinoside (Ara-C) in the elderly patients with hematological malignancy treated by Ara-C or cytarabine ocfosfate (SPAC)]. 759 61

Abnormalities of chromosome 16 in AML include del(16q), inv(16) and t(16;16). These three groups have been categorized together and have been associated with high complete remission (CR) and survival rates following Ara-C-based chemotherapy. We have reviewed the 63 AML or MDS patients with an abnormality of chromosome 16 treated at MD Anderson Cancer Center (MDACC) over the past 18 years. Marked differences in survival and remission duration (RD) were noted between the inv(16) or t(16;16) patients and those with del(16q), whose outcome was no better than other M4 AML or MDS patients treated during the same period. Other differences characterizing del(16q) included a lack of CNS relapses, lower incidences of eosinophilia and M4 FAB subtype. Half the inv(16) patients had additional karyotypic abnormalities. The overall survival and remission duration for those patients were no different from those for patients with inv(16) alone, although the probability of remaining in first CR at 2 years was higher in the inv(16) alone group. There was no difference in overall survival for the 45 patients who received HDAC vs those who did not. The incidence of CNS relapse was, however, markedly reduced for the HDAC patients. Eosinophilia did not correlate with improved survival. We conclude that del(16q) confers a different prognosis from inv(16) and t(16;16) and for the purposes of prognostication or treatment recommendations should no longer be categorized with them. Additional karyotypic changes however, which accompany inv(16) in 50% of cases do not influence the overall outcome compared to patients with inv(16) alone.
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PMID:Cytogenetic and clinical correlates in AML patients with abnormalities of chromosome 16. 759 86

We looked for bcl-2 protein expression by immunocytochemistry on bone marrow slides from 51 cases of myelodysplastic syndrome (MDS), of whom 25 received some form of chemotherapy. Forty-six of them had at least 20% bcl-2 positive blasts and the median percentage of positive blasts was 80%, whereas myeloid cells beyond blasts were always negative. No correlation was found between bcl-2 expression and the FAB type of MDS, CD34 expression and P-glycoprotein expression. A strong correlation between weak bcl-2 expression and the presence of a p53 mutation detected by SSCP analysis and direct sequencing was found. Response to chemotherapy (intensive chemotherapy or low-dose Ara-C) and survival were not significantly influenced by the intensity of bcl-2 expression in blasts, although there was a trend for better response to chemotherapy and longer survival in patients with strong bcl-2 expression. This trend was no longer found, however, if patients with a p53 mutation were excluded. Our findings show that blasts from a majority of MDS cases have bcl-2 expression and that strong bcl-2 expression is not associated with a poor prognosis. The correlation between weak bcl-2 expression and p53 mutation suggests a possible downregulation of bcl-2 gene expression by mutated p53, the mechanism of which remains to be established.
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PMID:bcl-2 expression in myelodysplastic syndromes and its correlation with hematological features, p53 mutations and prognosis. 772 10

Prolonged administration of conventional (100 mg/m2/day) or low dose Ara-C (20 mg/m2/day) has been associated with significant clinical antileukemic effects in AML and myelodysplastic syndromes. These doses and schedules of Ara-C yield plasma Ara-C concentrations in the range of 10 to 100 nM. Utilizing concentrations and a schedule of Ara-C treatment, representative of Ara-C exposures in these clinical situations, we performed in vitro studies to examine the effects of co-treatment with pIXY 321 on Ara-C induced apoptosis and Ara-C-mediated colony growth inhibition of human myeloid leukemia HL-60 cells. Significantly greater internucleosomal DNA fragmentation, higher percentage of morphologically recognizable apoptotic cells and increased colony growth inhibition were observed following treatment with 100 versus 10 nM Ara-C for 5 days. Simultaneous exposure to 10 ng/ml pIXY 321 resulted in significantly increased colony growth inhibition as well as DNA fragmentation and apoptosis due to 10 nM but not 100 nM Ara-C. These concentrations of Ara-C inhibited c-myc and did not induce c-jun mRNA expression. These effects of Ara-C on c-myc and c-jun expressions were not influenced by co-treatment with pIXY 321. Neither treatment with pIXY 321 or Ara-C alone, nor co-treatment with pIXY 321 and Ara-C, significantly altered the intracellular p26BCL-2 levels in HL-60 cells. These results indicate that co-treatment with pIXY 321 significantly increases low dose Ara-C-induced apoptosis and thereby its antileukemic activity.
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PMID:Combined antileukemic activity of pIXY 321 and Ara-C against human acute myeloid leukemia cells. 787 2

A 65-year-old female with acute myelomonocytic leukemia (AMMoL) developed from myelodysplastic syndrome (MDS), successfully treated with cytarabine ocfosfate (SPAC) is reported. Ubenimex, calcitriol and corticosteroid had a minor effect on her MDS. Since she had severe anemia and congestive heart failure on developing leukemia, she was treated with oral administration of SPAC, a cytidine deaminase resistant derivative of Ara-C. After the second course of SPAC (200 mg/day, for 14-28 days), marked erythroid bursts were found and she entered complete remission. The samplings of SPAC and its metabolites of SPAC were investigated in 2 cases including this case, but there seemed to be no relation between their content and effects. In AML patients, especially in cases developed from MDS, SPAC might be useful because it can be given orally even in an outpatient.
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PMID:[Successful treatment of acute myelomonocytic leukemia developed from MDS with cytarabine ocfosfate (SPAC)]. 788 Jan 11

Conventional-dose Ara-C (200 mg/m2 d 1-5) combined with idarubicin (12 mg/m2 d 1-3) was employed as remission induction and consolidation therapy in 23 elderly AML patients with a median age of 66 years (range, 60-75) with AML according to the FAB criteria (M1 n = 3, M2 n = 10, M4 n = 6, M5 n = 2, M6 n = 2), eligible for the study. In seven patients earlier MDS had been documented by previous bone marrow aspirates. The CR rate after one induction course was 65% (15/23). Toxicity was acceptable, with four patients dying during the chemotherapy-induced hypoplasia (4/23). Although 80% of the CR patients received two additional cycles of Ara-C and idarubicin as consolidation therapy, only two patients are still in continuous complete remission more than 12 months after achieving CR. The median disease-free survival of the CR patients was 11.5 months and the median survival of the entire group was 10 months. We conclude that conventional dose Ara-C/idarubicin is an effective protocol for inducing complete remission in elderly patients with AML, but that consolidation therapy consisting of two courses of the same regimen does not produce a relevant rate of long-term disease-free survival.
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PMID:Results of conventional-dose cytosine arabinoside and idarubicin in elderly patients with acute myeloid leukemia. 803 33

Allogeneic BMT is the treatment of choice for patients with MDS or sAML, offering a good chance of long-term disease-free survival if the transplant is performed in an early stage of disease or if the patient receives the transplant in complete remission after polychemotherapy. The transplant is limited to a minority of relatively young patients (aged below 55 years) with an HLA-identical sibling. Allogeneic BMT may also be considered when a closely- or fully-matched unrelated donor has been identified for a young and fit patient. All patients, including those without an excess of blasts, should be conditioned with bone marrow ablative therapy rather than an immune suppressive regime, such as cyclophosphamide alone. For the majority of patients there is no standard therapy other than appropriate supportive care. Relatively young patients below the age of 60 years with poor risk features can be considered for treatment with combination chemotherapy. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT could be treated with post-remission chemotherapy or autologous BMT in the framework of prospective studies. Older patients can be considered for treatment with haematopoietic growth factors alone or in combination with differentiating agents such as low-dose Ara-C. This treatment should be delivered within the context of carefully designed and conducted trials.
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PMID:New treatment approaches for myelodysplastic syndrome and secondary leukaemias. 807 47

Fifty consecutive adult patients with acute lymphoblastic leukemia (ALL) were treated with an intensive cyclical chemotherapy and the mean received dose of individual cytotoxic drug was retrospectively studied. The median age was 28 years. Twenty-one (43%) had white blood cell (WBC) count over 30 x 10(9)/l. Of the 26 patients with successful cytogenetic studies, ten (28%) had unfavorable clonal chromosomal abnormalities (four Philadelphia chromosome, six others). A high complete remission (CR) rate (86%) was achieved. This was associated with delivery of 100% of the planned dosage of vincristine, prednisone, and daunorubicin at induction. Dose reduction of asparaginase, the fourth drug in the induction protocol, was recorded in 20 (40%) patients. The CR rate of these patients was not adversely affected. Dose reduction was recorded during consolidation (38 of 43 remitters) and maintenance (18 of 20 remitters) as a result of treatment toxicity. The mean received dose of teniposide, Ara-C, asparaginase, mercaptopurine, and methotrexate was 73% (SD 7%), 73% (SD 7%), 62% (SD 41%), 65% (SD 15%) and 73% (SD 17%) of the planned dosage, respectively. The 5-year overall survival and leukemia-free survival (LFS) were 11% (95% CI: 0-27%) and 13% (95% CI: 0-26%), respectively. Even standard-risk patients had 4-year LFS of only 26% (95% CI: 0-57%). Among 36 remitters not withdrawn from consolidation, there were 29 treatment failures after a median follow-up of 42 months; 25 (86%) of these were leukemia relapse, three (10%) were toxic death during consolidation, and one patient (4%) died from therapy-related myelodysplastic syndrome. We postulate inadequate drug delivery during postremission therapy contributed to the high relapse rate in the whole group as well as the standard-risk patients.
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PMID:Poor outcome of intensive chemotherapy for adult acute lymphoblastic leukemia: a possible dose effect. 776 60

Forty-five patients with untreated, de novo acute myeloid leukemia (AML) were treated with high-dose cytosine arabinoside (Ara-C) plus mitoxantrone or daunorubicin. Forty-two patients entered complete remission with recovery of normal blood counts. Seven of these patients were excluded from further analysis (two, early consolidation chemotherapy; four, early relapse; one, hypersplenism). Of the remaining 35 patients, 20 (57%) developed thrombocytopenia and anemia (with or without neutropenia) a median of 3 weeks after entering complete remission. Post-remission cytopenias were more common in patients receiving mitoxantrone (81%) compared to those receiving daunorubicin (37%; p < 0.003). The cytopenias lasted a median of 54 days. Four of five patients in whom the cytopenias did not recover received mitoxantrone. Leukemia relapse or myelodysplasia did not explain these cytopenias. Post-remission cytopenias resulted in a greater than 90-day delay or prevention of planned autologous bone marrow transplantation in 13 of 17 otherwise eligible patients. We conclude that post-remission cytopenias are common following blood count recovery in AML patients entering complete remission with high-dose Ara-C and mitoxantrone or daunorubicin. Post-remission cytopenias do not necessarily imply leukemia relapse.
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PMID:Post-remission cytopenias following intense induction chemotherapy for acute myeloid leukemia. 815 48


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