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)

Myelodysplastic syndromes (MDS) are heterogeneous diseases. Patients with blast counts of more than 20% of nucleated bone marrow cells have a high risk of short survival. We treated six patients with refractory anemia with excess of blast in transformation (RAEBiT) with low dose cytosine arabinoside (LD Ara-C). We had one partial remission (PR), surviving 16 weeks and two complete remissions (CR), surviving 22 and 55+ months. Myelosuppression was dominant in all patients, but was not as serious as with conventional remission-induction treatments for leukemias. Bone marrow aplasia occurred in all responding patients, but a differentiation effect is possible too. Maintenance therapy with LD Ara-C may be important for the two long-lasting CR.
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PMID:Low dose cytosine arabinoside in refractory anemia with excess of blasts in transformation. 320 93

Responses have been reported in patients with myelodysplastic syndromes (MDS) after low-dose cytarabine (Ara-C) or 13-cis-retinoic acid (13-CRA) therapy. Recently, combination of these two substances in vitro was shown to produce a synergistic effect on differentiation of leukemic cells. We conducted a phase II trial with low-dose Ara-C (5 mg/m2 per 12 h s.c.) and 13-CRA (60 mg/m2 per day orally) in 14 patients with MDS, six of whom had refractory anemia with excess of blasts (RAEB), seven had RAEB in transformation (RAEBt) and one chronic myelomonocytic leukemia (CMML). The drugs were administered from day 1 to 14 and the treatment courses repeated every 4 to 8 weeks. One partial response and one minor response could be achieved. Major toxicity included dry skin, mucositis and cheilitis in 11 of the 14 patients. The response rate is no better than the results reported in the literature with either drugs alone. As yet there is no satisfactory treatment for MDS.
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PMID:Combination of low-dose cytarabine and 13-cis retinoic acid in the treatment of myelodysplastic syndromes. 332 May 77

A small group of elderly male patients received attenuated doses of daunomycin, cytosine arabinoside (Ara-C), and 6-thioguanine for treatment of myelodysplastic syndrome (MDS). Three patients had refractory anemia with excess blasts (RAEB), and two had chronic myelomonocytic leukemia (CMMoL). All five patients had developed severe transfusion requirements for platelets and red blood cells before therapy was begun. One patient developed necrosis of the cecum and expired 19 days after therapy, but the other four all showed substantial benefit from treatment. Three of those patients received multiple courses of chemotherapy which led to improvement in peripheral blood counts in each case. Duration of responses as noted by improvement in peripheral blood counts compared to pretreatment levels ranged from 1.5 to 9 months. Despite considerable improvement in peripheral blood parameters, some of the abnormal morphologic features of MDS persisted after each course of chemotherapy. These results obtained with attenuated chemotherapy schedules in a small group of patients are sufficiently encouraging to warrant an expanded phase II trial, which is under way at the University of Rochester Cancer Center.
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PMID:Effectiveness of attenuated chemotherapy in myelodysplastic syndromes: a preliminary report. 335 33

62 evaluable patients with myelodysplastic syndromes (MDS) or acute leukemia were treated with different combinations of low dose ara-C, alpha-interferon (IFN), 1 alpha-hydroxyvitamin D3 (vit D3) and retinoic acid. The aim was to study the efficacy and toxicity of each combination. The overall rate was 44%. Of these, 50% responded favorably to the combination of IFN, vit D3 and retinoic acid (IDR), which was comparable to the response rate of 43% for low-dose ara-C. The results of the IDR treatment may be explained by additive or synergistic effects between the separate drugs in the combination. Ara-C and IDR treatment was generally well-tolerated but interferon gave more side effects than any other drug used in the study. Evaluation of the full combination of ara-C, IFN, vit D3 and retinoic acid was not possible because of toxicity. Marrow hypoplasia was infrequent (5/27 patients) in cases responding favorably to treatment. Complete remissions were not longer than partial remissions or significant responses.
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PMID:Therapeutic effects of low-dose cytosine arabinoside, alpha-interferon, 1 alpha-hydroxyvitamin D3 and retinoic acid in acute leukemia and myelodysplastic syndromes. 337 98

This study was designed to evaluate the effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome (MDS). The subjects were 33 patients (19 acute myelocytic leukemia (AML), 9 MDS, 3 atypical leukemia and 2 unclassified leukemia). The age range was 19 to 84 years with a mean age of 51.5 years. We administered low-dose Ara-C (5-10 mg/m2/12 h s.c. or i.v.) for 13 to 35 days with a mean of 16.7 days. Complete remission and partial remission were obtained in 8 of 31 (25.8%) and in 9 of 31 (29.0%) respectively. A high response rate was found in M2 types showing a tendency for mature and refractory anemia with excess blasts in MDS according to the FAB classification. In our cases, severe pancytopenia in peripheral blood as a result of Ara-C was observed before normal hematopoiesis recurred. From the above results, the mechanism of low-dose Ara-C may induce remission by a cytotoxic rather than a differentiation effect. This treatment can be offered to patients with refractory, atypical leukemia and MDS with limited toxicity.
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PMID:[Effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome]. 345 53

The bone marrow smears and marrow biopsies of 30 unselected consecutive patients with a myelodysplastic syndrome have been classified retrospectively according to the proposals of the French-American-British cooperative group (FAB). The diagnoses according to the FAB classification were refractory anemia (RA) in 3, RA with ring sideroblasts (RAS) in 5, RA with excess of blasts (RAEB) in 14, REAB in transformation (RAEB-t) in 5, and chronic myelomonocytic leukemia (CMML) in 3. The group comprised 19 men and 11 women with a median age of 68 years. Of 22 patients, 9 died after progression to acute non lymphoblastic leukemia (ANLL), 7 from infections, 2 from bleeding and 4 from unrelated causes. Actuarial survival is 10.5 months, 8 patients being at risk at the time of evaluation. Although the small number of patients does not allow statistical evaluation, our results are similar to those in the literature: prognosis is less good with an increasing number of marrow blasts and degree of cytopenia, and the risk of progression to ANLL is higher for REAB-t and REAB patients. Of 4 patients treated with small doses of cytosine-arabinoside (Ara-C), one responded and remained stable without treatment for 7 months. 2 patients resistant to small-dose Ara-C showed complete response to subsequent high-dose Ara-C treatment.
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PMID:[Retrospective study of 30 cases of myelodysplastic syndrome according to the French-American-British classification]. 346 10

Four patients with acute myeloid leukemia (AML) and three with myelodysplastic syndrome (MDS) were given low dose cytosine arabinoside (Ara-C) therapy. One patient with de novo AML and two patients having refractory anemia with excess of blasts (RAEB) achieved responses. Although the responses lasted for only a short duration (2-3 months), the therapy was well tolerated and not accompanied by severe complications, while severe cytopenia was a frequent side effect with transfusions being necessary in most patients. This therapy could be clinically effective for certain types of AML and MDS (especially RAEB and RAEB in transformation).
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PMID:Low dose cytosine arabinoside therapy in myelodysplastic syndrome and acute myeloid leukemia. 347 89

The effect of a small dose of aclacinomycin-A (ACR) was examined in two patients with refractory anemia (RA) and two with refractory anemia with excess of blasts in transformation (RAEB-t). ACR (7 or 14 mg/m2) was given for 10 days in a 2-h per day drip infusion. Clinical symptoms and laboratory data improved in 3 of these 4 patients. In a patient with RA, marked increase in reticulocytes and elevation of the hemoglobin level from 6 to 9 g/dl was observed after two courses of ACR therapy. In two with RAEB-t, Auer's rod bearing cells disappeared in the bone marrow and megaloblastic change of the erythroblasts was diminished in one patient. Hemoglobin levels rose from 4.7 to 10 g/dl in one, and platelets and WBC increased in another. No effect was seen in a patient with RA. The cytoreductive effect of ACR was minor compared to the therapy with small dose of cytosine arabinoside (Ara-C). Therefore, ACR warrants further consideration for the treatment of patients with MDS.
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PMID:Treatment of four patients with myelodysplastic syndrome with a small dose of aclacinomycin-A. 347 62

Twenty-one patients with refractory acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndrome were treated with low-dose cytosine arabinoside (LDARC). LDARC was administered by subcutaneous injection every 12 hours at a dose of 10 mg/m2 (regimen A) or at a dose of 20 mg/m2 by continuous intravenous infusion (CIV) or continuous subcutaneous injection (CSC) (regimen B). Among 22 courses, two elderly patients with ANLL (M4 and M5) and one M4 patient with myelofibrosis obtained complete remission (CR) and three elderly patients with ANLL (one M1 and two M2) and one patient with ANLL developed from RAEB in transformation obtained partial remission (PR). The overall remission rate (CR + PR) was 31.8%. The CR durations were 2.5, 5 and 2 months, respectively. The plasma concentration of Ara-C determined in regimen B was 8.26 +/- 4.12 ng/ml. There was no difference in the plasma concentration of Ara-C between CIV and CSC. We consider that the major mode of action of LDARC lies in its cytotoxic effect, since all patients who obtained remission exhibited pancytopenia and bone marrow hypoplasia. However, in several patients, we observed transient monocytosis and granulocytosis which were considered to be suggestive evidence of differentiation of leukemia cells.
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PMID:[The clinical effect of low-dose Ara-C in patients with refractory acute nonlymphocytic leukemia and myelodysplastic syndrome]. 356 2

Low-dose Ara-C (10 mg/m2 subcutaneously bid) has been used as an alternative therapy for acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes. We sought to define its therapeutic mechanism by assessing clinical and cytogenetic responses to treatment in conjunction with careful in vitro study of both morphologic and functional characteristics of bone marrow cells cultured with Ara-C. Sixteen patients (12 ANLL, four myelodysplastic syndrome) were treated. All developed pancytopenia and 11 of 12 had bone marrow hypoplasia during treatment. Four had a meaningful clinical response while five more showed in vivo leukemic cell sensitivity to low-dose Ara-C. Seven showed no response. Cells with cytogenetic abnormalities were either decreased in number or eradicated during clinical improvement. Liquid culture of marrow mononuclear cells with Ara-C (.033-.333 micrograms/ml X 7 days) produced little evidence of morphologic or functional differentiation (ten of 11 studied). No functional maturation was observed in cells from clinically responding patients. We conclude that low-dose Ara-C is modestly effective for some patients with ANLL or myelodysplasia. However, no evidence for in vivo leukemic differentiation is suggested by either in vitro culture studies or cytogenetic correlates of clinical response. In vitro marrow culture studies failed to predict clinical response to Ara-C.
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PMID:In vitro correlates of low dose ara-C efficacy: clinical, cytogenetic, and bone marrow culture analysis. 357 63


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